EPCAM; epithelial cell adhesion molecule (2p21)

Gene Summary

Gene:EPCAM; epithelial cell adhesion molecule
Aliases: ESA, KSA, M4S1, MK-1, DIAR5, EGP-2, EGP40, KS1/4, MIC18, TROP1, EGP314, HNPCC8, TACSTD1
Summary:This gene encodes a carcinoma-associated antigen and is a member of a family that includes at least two type I membrane proteins. This antigen is expressed on most normal epithelial cells and gastrointestinal carcinomas and functions as a homotypic calcium-independent cell adhesion molecule. The antigen is being used as a target for immunotherapy treatment of human carcinomas. Mutations in this gene result in congenital tufting enteropathy. [provided by RefSeq, Dec 2008]
Databases:OMIM, VEGA, HGNC, Ensembl, GeneCard, Gene
Protein:epithelial cell adhesion molecule
Updated:14 December, 2014


What does this gene/protein do?
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Cancer Overview

Research Indicators

Publications Per Year (1989-2014)
Graph generated 14 December 2014 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

Tag cloud generated 14 December, 2014 using data from PubMed, MeSH and CancerIndex

Notable (8)

Scope includes mutations and abnormal protein expression.

Entity Topic PubMed Papers
Colorectal CancerEPCAM and Colorectal Cancer View Publications46
Breast CancerEPCAM and Breast Cancer View Publications45
Hereditary Nonpolyposis Colorectal Cancer EPCAM and Hereditary Nonpolyposis Colorectal Cancer (HNPCC) View Publications25
Liver CancerEPCAM and Liver Cancer View Publications24
Pancreatic CancerEPCAM and Pancreatic Cancer View Publications17
Lung CancerEPCAM and Lung Cancer View Publications15
Ovarian CancerEPCAM and Ovarian Cancer View Publications12
Stomach CancerEPCAM and Stomach Cancer View Publications8

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Related Links

Latest Publications: EPCAM (cancer-related)

Balci TB, Prykhozhij SV, Teh EM, et al.
A transgenic zebrafish model expressing KIT-D816V recapitulates features of aggressive systemic mastocytosis.
Br J Haematol. 2014; 167(1):48-61 [PubMed] Related Publications
Systemic mastocytosis (SM) is a rare myeloproliferative disease without curative therapy. Despite clinical variability, the majority of patients harbour a KIT-D816V mutation, but efforts to inhibit mutant KIT with tyrosine kinase inhibitors have been unsatisfactory, indicating a need for new preclinical approaches to identify alternative targets and novel therapies in this disease. Murine models to date have been limited and do not fully recapitulate the most aggressive forms of SM. We describe the generation of a transgenic zebrafish model expressing the human KIT-D816V mutation. Adult fish demonstrate a myeloproliferative disease phenotype, including features of aggressive SM in haematopoeitic tissues and high expression levels of endopeptidases, consistent with SM patients. Transgenic embryos demonstrate a cell-cycle phenotype with corresponding expression changes in genes associated with DNA maintenance and repair, such as reduced dnmt1. In addition, epcam was consistently downregulated in both transgenic adults and embryos. Decreased embryonic epcam expression was associated with reduced neuromast numbers, providing a robust in vivo phenotypic readout for chemical screening in KIT-D816V-induced disease. This study represents the first zebrafish model of a mast cell disease with an aggressive adult phenotype and embryonic markers that could be exploited to screen for novel agents in SM.

Related: Apoptosis

Fan QM, Jing YY, Yu GF, et al.
Tumor-associated macrophages promote cancer stem cell-like properties via transforming growth factor-beta1-induced epithelial-mesenchymal transition in hepatocellular carcinoma.
Cancer Lett. 2014; 352(2):160-8 [PubMed] Related Publications
Tumor-associated macrophages (TAMs), a crucial component of immune cells infiltrated in tumor microenvironment, have been found to be associated with progression and metastasis of hepatocellular carcinoma (HCC). In this study, we aimed to clarify the mechanism underlying the crosstalk between TAMs and cancer stem cells (CSCs) in HCC. Mouse macrophage cell line RAW264.7 cells were used to investigate the effects of TAMs on mouse hepatoma cell line Hepa1-6 cells in vivo and vitro. A total of 90 clinical samples had pathology-proven HCC were used to evaluate the distribution of TAMs and CSCs and analyze their value in predicting the prognosis. In the study, we have found that the number of TAMs has a positive correlation with the density of CSCs in the marginal of human HCC. Our results show that, cocultured with TAM-conditioned medium (CM) promoted CSC-like properties in Hepa1-6 cells, which underwent EMT and gained higher invasive capability. TAMs secreted more transforming growth factor- beta1 (TGF-beta1) than other phenotypes of macrophage. Furthermore, depletion of TGF-beta1 blocked acquisition of CSC-like properties by inhibition of TGF-beta1-induced EMT. High expression of CD68 in the EpCAM positive expression HCC tissues was strongly associated with both poor cancer-free survival and overall survival in patients. Our results indicate that the TAMs promote CSC-like properties via TGF-beta1-induced EMT and they may contribute to investigate the prognosis of HCC.

Related: Liver Cancer Signal Transduction TGFB1

Goossens-Beumer IJ, Zeestraten EC, Benard A, et al.
Clinical prognostic value of combined analysis of Aldh1, Survivin, and EpCAM expression in colorectal cancer.
Br J Cancer. 2014; 110(12):2935-44 [PubMed] Article available free on PMC after 10/06/2015 Related Publications
BACKGROUND: Tumour aggressiveness might be related to the degree of main cancer hallmark acquirement of tumour cells, reflected by expression levels of specific biomarkers. We investigated the expression of Aldh1, Survivin, and EpCAM, together reflecting main cancer hallmarks, in relation to clinical outcome of colorectal cancer (CRC) patients.
METHODS: Immunohistochemistry was performed using a tumour tissue microarray of TNM (Tumour, Node, Metastasis)-stage I-IV CRC tissues. Single-marker expression or their combination was assessed for associations with the clinical outcome of CRC patients (N=309).
RESULTS: Increased expression of Aldh1 or Survivin, or decreased expression of EpCAM was each associated with poor clinical outcome, and was therefore identified as clinically unfavourable expression. Analyses of the combination of all three markers showed worse clinical outcome, specifically in colon cancer patients, with an increasing number of markers showing unfavourable expression. Hazard ratios ranged up to 8.3 for overall survival (P<0.001), 36.6 for disease-specific survival (P<0.001), and 27.1 for distant recurrence-free survival (P<0.001).
CONCLUSIONS: Our data identified combined expression levels of Aldh1, Survivin, and EpCAM as strong independent prognostic factors, with high hazard ratios, for survival and tumour recurrence in colon cancer patients, and therefore reflect tumour aggressiveness.

Related: Colorectal (Bowel) Cancer BIRC5

Miao L, Xiong X, Lin Y, et al.
Down-regulation of FoxM1 leads to the inhibition of the epithelial-mesenchymal transition in gastric cancer cells.
Cancer Genet. 2014; 207(3):75-82 [PubMed] Related Publications
Emerging evidence suggests that FoxM1 may have a crucial role in the development and progression of human gastric cancer. Therefore, we sought to determine the role of FoxM1 in gastric cancer epithelial-mesenchymal transition (EMT). The down-regulation of FoxM1 expression by the transfection of cells with FoxM1 siRNA decreased cell migration, invasion, and proliferation. Moreover, the over-expression of FoxM1 promoted cell migration, invasion, and proliferation, which led to the acquisition of an EMT phenotype by up-regulating the protein expression of the mesenchymal cell markers ZEB1, ZEB2, and vimentin and by down-regulating the epithelial cell marker E-cadherin in gastric epithelial cells. More important, the depletion of FoxM1 levels in gastric cancer cells led to significant decreases in the NF-κB p65 subunit, cyclin D1, Hes-1, VEGF, and EpCAM protein levels. Real-time PCR examination showed that the down-regulation of FoxM1 expression significantly inhibited vimentin and N-cadherin expression compared to that in control cells. Most important, cells transfected with FoxM1 siRNA displayed an elongated/irregular fibroblastoid morphology and reduction of the vimentin expression. Our current study strongly suggests that FoxM1 signaling has important roles in tumor cell aggressiveness through the acquisition of the EMT phenotype in gastric cancer cells.

Related: Stomach Cancer Gastric Cancer FOXM1

Bao B, Azmi AS, Aboukameel A, et al.
Pancreatic cancer stem-like cells display aggressive behavior mediated via activation of FoxQ1.
J Biol Chem. 2014; 289(21):14520-33 [PubMed] Article available free on PMC after 23/05/2015 Related Publications
Subpopulations of cancer stem cells (CSCs) or cancer stem-like cells (CSLCs) have been identified from most tumors, including pancreatic cancer (PC), and the existence of these cells is clinically relevant. Emerging evidence suggests that CSLCs participate in cell growth/proliferation, migration/invasion, metastasis, and chemo-radiotherapy resistance, ultimately contributing to poor clinical outcome. However, the pathogenesis and biological significance of CSLCs in PC has not been well characterized. In the present study, we found that isolated triple-marker-positive (CD44(+)/CD133(+)/EpCAM(+)) cells of human PC MiaPaCa-2 and L3.6pl cells behave as CSLCs. These CSLCs exhibit aggressive behavior, such as increased cell growth, migration, clonogenicity, and self-renewal capacity. The mRNA expression profiling analysis showed that CSLCs (CD44(+)/CD133(+)/EpCAM(+)) exhibit differential expression of more than 1,600 mRNAs, including FoxQ1, compared with the triple-marker-negative (CD44(-)/CD133(-)/EpCAM(-)) cells. The knockdown of FoxQ1 by its siRNA in CSLCs resulted in the inhibition of aggressive behavior, consistent with the inhibition of EpCAM and Snail expression. Mouse xenograft tumor studies showed that CSLCs have a 100-fold higher potential for tumor formation and rapid tumor growth, consistent with overexpression of CSC-associated markers/mediators, including FoxQ1, compared with its parental MiaPaCa-2 cells. The inhibition of FoxQ1 attenuated tumor formation and growth, and expression of CSC markers in the xenograft tumor derived from CSLCs of MiaPaCa-2 cells. These data clearly suggest the role of differentially expressed genes in the regulation of CSLC characteristics, further suggesting that targeting some of these genes could be important for the development of novel therapies for achieving better treatment outcome of PC.

Related: Apoptosis Cancer of the Pancreas Pancreatic Cancer

Xu Y, Zhao H, Hou J
Correlation between overexpression of EpCAM in prostate tissues and genesis of androgen-dependent prostate cancer.
Tumour Biol. 2014; 35(7):6695-700 [PubMed] Related Publications
The objective of this study was to investigate the role of epithelial cell adhesion molecule (EpCAM) in the genesis and the progress of prostate cancer, especially of castration-resistant prostate cancer. Protein expression of EpCAM in ten pairs of prostate cancer tissues and normal adjacent tissues, plus three cell lines, was examined. Short hairpin RNA (shRNA) interference technique was employed to silence the expression of EpCAM in prostate cancer cell LNCaP and construct a stable transfected cell line. In vitro assay was conducted to analyze the effect of EpCAM expression on the expressions of Androgen receptor (AR), Prostate specific antigen (PSA), and cellular proliferation and invasion. EpCAM was found significantly expressed higher in prostate cancer tissues than in normal adjacent tissues. In three cell lines (DU-145, PC-3, and LNCaP), the expression of EpCAM in LNCaP, androgen-dependent prostate cancer cells, was significantly higher than that in the other two. As EpCAM was silenced in LNCaP, the expression levels of AR and PSA obviously descended, and cellular abilities of proliferation and invasion were obviously inhibited.The overexpression of EpCAM has correlation with the genesis of prostate cancer, especially androgen-dependent prostate cancer. As the expression of AR is facilitated, prostate cancer cells' abilities to proliferate and invade are consequently enhanced.

Related: Prostate Cancer AR: androgen receptor

Villa-Morales M, Cobos MA, González-Gugel E, et al.
FAS system deregulation in T-cell lymphoblastic lymphoma.
Cell Death Dis. 2014; 5:e1110 [PubMed] Article available free on PMC after 23/05/2015 Related Publications
The acquisition of resistance towards FAS-mediated apoptosis may be required for tumor formation. Tumors from various histological origins exhibit FAS mutations, the most frequent being hematological malignancies. However, data regarding FAS mutations or FAS signaling alterations are still lacking in precursor T-cell lymphoblastic lymphomas (T-LBLs). The available data on acute lymphoblastic leukemia, of precursor origin as well, indicate a low frequency of FAS mutations but often report a serious reduction in FAS-mediated apoptosis as well as chemoresistance, thus suggesting the occurrence of mechanisms able to deregulate the FAS signaling pathway, different from FAS mutation. Our aim at this study was to determine whether FAS-mediated apoptotic signaling is compromised in human T-LBL samples and the mechanisms involved. This study on 26 T-LBL samples confirms that the FAS system is impaired to a wide extent in these tumors, with 57.7% of the cases presenting any alteration of the pathway. A variety of mechanisms seems to be involved in such alteration, in order of frequency the downregulation of FAS, the deregulation of other members of the pathway and the occurrence of mutations at FAS. Considering these results together, it seems plausible to think of a cumulative effect of several alterations in each T-LBL, which in turn may result in FAS/FASLG system deregulation. Since defective FAS signaling may render the T-LBL tumor cells resistant to apoptotic cell death, the correct prognosis, diagnosis and thus the success of anticancer therapy may require such an in-depth knowledge of the complete scenario of FAS-signaling alterations.

Related: TNFRSF6 gene Apoptosis Signal Transduction

Nunna S, Reinhardt R, Ragozin S, Jeltsch A
Targeted methylation of the epithelial cell adhesion molecule (EpCAM) promoter to silence its expression in ovarian cancer cells.
PLoS One. 2014; 9(1):e87703 [PubMed] Article available free on PMC after 23/05/2015 Related Publications
The Epithelial Cell Adhesion Molecule (EpCAM) is overexpressed in many cancers including ovarian cancer and EpCAM overexpression correlates with decreased survival of patients. It was the aim of this study to achieve a targeted methylation of the EpCAM promoter and silence EpCAM gene expression using an engineered zinc finger protein that specifically binds the EpCAM promoter fused to the catalytic domain of the Dnmt3a DNA methyltransferase. We show that transient transfection of this construct increased the methylation of the EpCAM promoter in SKOV3 cells from 4-8% in untreated cells to 30%. Up to 48% methylation was observed in stable cell lines which express the chimeric methyltransferase. Control experiments confirmed that the methylation was dependent on the fusion of the Zinc finger and the methyltransferase domains and specific for the target region. The stable cell lines with methylated EpCAM promoter showed a 60-80% reduction of EpCAM expression as determined at mRNA and protein level and exhibited a significantly reduced cell proliferation. Our data indicate that targeted methylation of the EpCAM promoter could be an approach in the therapy of EpCAM overexpressing cancers.

Related: Ovarian Cancer

Winer-Jones JP, Vahidi B, Arquilevich N, et al.
Circulating tumor cells: clinically relevant molecular access based on a novel CTC flow cell.
PLoS One. 2014; 9(1):e86717 [PubMed] Article available free on PMC after 23/05/2015 Related Publications
BACKGROUND: Contemporary cancer diagnostics are becoming increasing reliant upon sophisticated new molecular methods for analyzing genetic information. Limiting the scope of these new technologies is the lack of adequate solid tumor tissue samples. Patients may present with tumors that are not accessible to biopsy or adequate for longitudinal monitoring. One attractive alternate source is cancer cells in the peripheral blood. These rare circulating tumor cells (CTC) require enrichment and isolation before molecular analysis can be performed. Current CTC platforms lack either the throughput or reliability to use in a clinical setting or they provide CTC samples at purities that restrict molecular access by limiting the molecular tools available.
METHODOLOGY/PRINCIPAL FINDINGS: Recent advances in magetophoresis and microfluidics have been employed to produce an automated platform called LiquidBiopsy®. This platform uses high throughput sheath flow microfluidics for the positive selection of CTC populations. Furthermore the platform quantitatively isolates cells useful for molecular methods such as detection of mutations. CTC recovery was characterized and validated with an accuracy (<20% error) and a precision (CV<25%) down to at least 9 CTC/ml. Using anti-EpCAM antibodies as the capture agent, the platform recovers 78% of MCF7 cells within the linear range. Non specific recovery of background cells is independent of target cell density and averages 55 cells/mL. 10% purity can be achieved with as low as 6 CTCs/mL and better than 1% purity can be achieved with 1 CTC/mL.
CONCLUSIONS/SIGNIFICANCE: The LiquidBiopsy platform is an automated validated platform that provides high throughput molecular access to the CTC population. It can be validated and integrated into the lab flow enabling CTC enumeration as well as recovery of consistently high purity samples for molecular analysis such as quantitative PCR and Next Generation Sequencing. This tool opens the way for clinically relevant genetic profiling of CTCs.

Danda R, Krishnan G, Ganapathy K, et al.
Targeted expression of suicide gene by tissue-specific promoter and microRNA regulation for cancer gene therapy.
PLoS One. 2013; 8(12):e83398 [PubMed] Article available free on PMC after 23/05/2015 Related Publications
In order to realise the full potential of cancer suicide gene therapy that allows the precise expression of suicide gene in cancer cells, we used a tissue specific Epithelial cell adhesion molecule (EpCAM) promoter (EGP-2) that directs transgene Herpes simplex virus-thymidine kinase (HSV-TK) expression preferentially in EpCAM over expressing cancer cells. EpCAM levels are considerably higher in retinoblastoma (RB), a childhood eye cancer with limited expression in normal cells. Use of miRNA regulation, adjacent to the use of the tissue-specific promoter, would provide the second layer of control to the transgene expression only in the tumor cells while sparing the normal cells. To test this hypothesis we cloned let-7b miRNA targets in the 3'UTR region of HSV-TK suicide gene driven by EpCAM promoter because let-7 family miRNAs, including let-7b, were found to be down regulated in the RB tumors and cell lines. We used EpCAM over expressing and let-7 down regulated RB cell lines Y79, WERI-Rb1 (EpCAM (+ve)/let-7b(down-regulated)), EpCAM down regulated, let-7 over expressing normal retinal Müller glial cell line MIO-M1(EpCAM (-ve)/let-7b(up-regulated)), and EpCAM up regulated, let-7b up-regulated normal thyroid cell line N-Thy-Ori-3.1(EpCAM (+ve)/let-7b(up-regulated)) in the study. The cell proliferation was measured by MTT assay, apoptosis was measured by probing cleaved Caspase3, EpCAM and TK expression were quantified by Western blot. Our results showed that the EGP2-promoter HSV-TK (EGP2-TK) construct with 2 or 4 copies of let-7b miRNA targets expressed TK gene only in Y79, WERI-Rb-1, while the TK gene did not express in MIO-M1. In summary, we have developed a tissue-specific, miRNA-regulated dual control vector, which selectively expresses the suicide gene in EpCAM over expressing cells.

Related: Breast Cancer Eye Cancer Retinoblastoma

Behnke MK, Reimers M, Fisher RA
Stem cell and hepatocyte proliferation in hepatitis C cirrhosis and hepatocellular carcinoma: transplant implications.
Ann Hepatol. 2013 Jan-2014 Feb; 13(1):45-53 [PubMed] Related Publications
BACKGROUND. The liver possesses two distinct mechanisms for healing. Wound healing via hepatic stem cells recapitulates early development (hepatoblast proliferation), while liver regeneration resembles late embryonic growth (hepatocyte proliferation). Loss of control over both of these processes have been proposed as mechanisms that may contribute to poor outcomes in HCC. MATERIAL AND METHODS. We used microarray gene expression profiles to examine the involvement of hepatic stem cell and hepatocyte proliferation markers and regulators in HCV-induced cirrhosis and HCC. We compared 30 cirrhosis and 49 HCC samples to 12 disease-free control livers. RESULTS. Cirrhosis and HCC expressed markers of stem cell. Inhibitors of hepatocyte proliferation (HP) were highly expressed in cirrhosis. Loss of these HP inhibitors in HCC patients was associated poor prognosis (94 vs. 38% 2-year recurrence- free survival, p = 0.0003). Principal Components Analysis discriminated cirrhotic and HCC tissues, and HCC patients with poor (< 2 year) vs. good (> 2 year) recurrence-free survival. Loss of CDH1 expression correlated with up-regulation of hepatocyte proliferation promoters MET and YAP1. CDH1, MET, and YAP1 were independent predictors of recurrence-free survival by Cox regression when corrected for tumor stage (p < 0.0001). CONCLUSION. HCV-cirrhosis is characterized by proliferation of liver stem cells and inhibition of hepatocyte proliferation. HCC tumors in which this pattern persists have superior outcomes to those which acquire a hepatocyte proliferation signature. Genes in this signature should be studied further for potential as tissue or serum biomarkers for patient risk stratification. CDH1 and MET are candidates for personalized therapies with targeted pharmaceutical agents.

Related: Liver Cancer MET gene CDH1 TACSTD2 (GA733)

Mikulová V, Cabiňaková M, Janatková I, et al.
Detection of circulating tumor cells during follow-up of patients with early breast cancer: Clinical utility for monitoring of therapy efficacy.
Scand J Clin Lab Invest. 2014; 74(2):132-42 [PubMed] Related Publications
INTRODUCTION: Circulating tumor cells (CTCs) detection prior to and during therapy is considered as an independent and strong prognostic marker. The present study was designed to isolate and characterize CTCs in peripheral blood of an early breast cancer (BC) patient as a biomarker for monitoring treatments efficacy.
MATERIALS AND METHODS: In total, 54 early breast cancer patients undergoing neoadjuvant and/or adjuvant chemotherapy regimens were enrolled into a prospective study. CTC detection in blood was performed by AdnaTest BreastCancer(™) (AdnaGen AG, Germany), which is based on the detection of EpCAM, HER2 and MUC1 specific transcripts in enriched CTC-lysates. Additionally, cDNA from isolated CTCs and PBMC was used for qPCR gene expression analysis of TOP1, TOP2A, CTSD, ST6, CK19 and reference gene actin.
RESULTS: We found that CTCs can be detected in the peripheral blood of approximately 31% of early stage breast cancer patients. The presence of CTCs was detected in 36% ER positive, 32% PR positive and 30% HER2 positive patients. We found no correlation between CTCs and tumor size, tumor grade, histological grade and receptor status. Only 7% of all patients remained CTCs positive after adjuvant therapy. Gene expression analysis revealed a particular heterogeneity of the studied genes.
CONCLUSIONS: In conclusion, CTC detection may be a promising early marker of disease progression potentially enhancing the difficult therapeutic decisions. Further studies should, however, clearly demonstrate its utility for both the prediction of outcome and monitoring the effect of treatment.

Related: Breast Cancer MUC1 gene

Sterlacci W, Savic S, Fiegl M, et al.
Putative stem cell markers in non-small-cell lung cancer: a clinicopathologic characterization.
J Thorac Oncol. 2014; 9(1):41-9 [PubMed] Related Publications
INTRODUCTION: The cancer stem cell (CSC) theory postulates the existence of a distinct population of undifferentiated cells responsible for tumor initiation and maintenance. CSCs may be naturally resistant to the cytotoxic effect of radio-chemotherapy because of slow cell cycling, lower proliferation, and increased expression of DNA repair and antiapoptosis genes. To date, a universal marker for CSCs has not been identified. Proposed CSC markers are expressed both by cancer cells as well as by benign stem cells. Although many putative CSC markers exist, a precise characterization for non-small-cell lung cancer (NSCLC) is lacking.
METHODS: We explored the expression of multiple alleged stemness associated markers in 371 surgically resected NSCLCs. Extensive clinical data and a postoperative follow-up period of up to 15 years enabled detailed clinicopathological correlations. ABCG5, ALDH1, CD24, CD44, CD133, CD166, epithelial cell adhesion molecule epitopes (ESA, MOC-31, Ber-EP4), nestin, OCT4, and sex-determining region Y-box 2 were analyzed immunohistochemically by using a standardized tissue microarray platform.
RESULTS: Sex-determining region Y-box 2, CD44, ABCG5, ALDH1, and nestin were associated with poorer tumor differentiation and/or an increased proliferation index. ALDH1, CD44, and SOX2 were frequently found in squamous cell carcinoma, whereas CD24, CD166, and epithelial cell adhesion molecule markers were encountered in adenocarcinomas. CD44 expression was an independent marker associated with better overall survival in squamous cell carcinoma and Ber-EP4 was associated with tumor recurrences.
CONCLUSION: The expression and prognostic significance of CSC markers obviously varies depending on histologic NSCLC subtype. Importantly, our findings suggest that CD44 and Ber-EP4 may be promising for ongoing targeted therapies in specific NSCLC subgroups.

Related: Non-Small Cell Lung Cancer Lung Cancer

Elesawy BH, Abd El hafez A, Shawky Ael-A, Arafa M
Immunohistochemistry-based subtyping of breast carcinoma in Egyptian women: a clinicopathologic study on 125 patients.
Ann Diagn Pathol. 2014; 18(1):21-6 [PubMed] Related Publications
Breast carcinoma is a heterogeneous disease affected by patients' ethnicity. Gene expression analysis identified several molecular subtypes, and similar subtyping has now been found to be feasible using immunohistochemistry. This study estimated the distribution of intrinsic breast cancer subtypes using estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (Her2/neu), and cytokeratin 5/6 immunostaining in a cohort of 125 Egyptian women diagnosed as having invasive breast carcinoma. Associations with clinicopathologic variables and the prognostic markers Bcl-2 and Cyclin D1 were investigated and statistically analyzed. Population difference in breast cancer subtypes was detected, suggesting etiologic and genetic heterogeneity among demographic groups. As reported worldwide, most tumors were luminal A (39.2%), but basal-like and unclassified subtypes had higher proportions among our cohort (16.8% and 16%, respectively), particularly in premenopausal patients (P = .0001), in contrast to postmenopausal African Americans, premenopausal European Americans, and other populations. Her2-overexpressing subtype was the least common subtype (13.65%) among our patients, although it is more common in Asians. Basal-like and unclassified carcinomas were more frequently grade 3 neoplasms (P = .035). Lobular histology was distributed among luminal A, B and unclassified subtypes (P = .006). The highest frequency of nodal positivity was associated with Her2 overexpressing carcinomas (94.1%, P = .0001). Luminal and unclassified carcinomas more likely expressed Bcl-2 (P = .011) and Cyclin D1 (P = .0001), whereas basal and Her2 subtypes had the lowest expression levels. Immunohistochemistry-based subtyping can be helpful in separating breast carcinoma into subtypes that vary in distribution among different populations. These subtypes have distinct clinicopathologic features and diverse prognostication, which may imply different therapeutic options for each subtype.

Related: Breast Cancer

Nishitani S, Horie M, Ishizaki S, Yano H
Branched chain amino acid suppresses hepatocellular cancer stem cells through the activation of mammalian target of rapamycin.
PLoS One. 2013; 8(11):e82346 [PubMed] Article available free on PMC after 23/05/2015 Related Publications
Differentiation of cancer stem cells (CSCs) into cancer cells causes increased sensitivity to chemotherapeutic agents. Although inhibition of mammalian target of rapamycin (mTOR) leads to CSC survival, the effect of branched chain amino acids (BCAAs), an mTOR complex 1 (mTORC1) activator remains unknown. In this study, we examined the effects of BCAA on hepatocellular carcinoma (HCC) cells expressing a hepatic CSC marker, EpCAM. We examined the effects of BCAA and/or 5-fluorouracil (FU) on expression of EpCAM and other CSC-related markers, as well as cell proliferation in HCC cells and in a xenograft mouse model. We also characterized CSC-related and mTOR signal-related molecule expression and tumorigenicity in HCC cells with knockdown of Rictor or Raptor, or overexpression of constitutively active rheb (caRheb). mTOR signal-related molecule expression was also examined in BCAA-treated HCC cells. In-vitro BCAA reduced the frequency of EpCAM-positive cells and improved sensitivity to the anti-proliferative effect of 5-FU. Combined 5-FU and BCAA provided better antitumor efficacy than 5-FU alone in the xenograft model. Stimulation with high doses of BCAA activated mTORC1. Knockdown and overexpression experiments revealed that inhibition of mTOR complex 2 (mTORC2) or activation of mTORC1 led to decreased EpCAM expression and little or no tumorigenicity. BCAA may enhance the sensitivity to chemotherapy by reducing the population of cscs via the mTOR pathway. This result suggests the utility of BCAA in liver cancer therapy.

Related: Apoptosis Liver Cancer Signal Transduction

Yoshida GJ, Saya H
EpCAM expression in the prostate cancer makes the difference in the response to growth factors.
Biochem Biophys Res Commun. 2014; 443(1):239-45 [PubMed] Related Publications
INTRODUCTION: Epithelial cell adhesion molecule (EpCAM) is expressed in tumors with an epithelial cell of origin, in a heterogeneous manner. Prostate cancer stem-like cells highly express EpCAM. However, little is known about how EpCAM is involved in the ability of cells to adapt to micro-environmental changes in available growth factors, which is one of the essential biological phenotypes of cancer stem-like cells (CSCs).
METHODS: EpCAM-high and EpCAM-low subpopulations of cells were established from the prostate cancer cell line PC-3. Signal transductions in response to serum starvation, and on the exposure to EGF ligand or the specific inhibitor were analyzed in terms. Furthermore, we analyzed the expression level of amino acid transporters which contribute to the activation of mTOR signal between the two subgroups.
RESULTS: EpCAM-high and EpCAM-low PC-3 subpopulations showed markedly different responses to serum starvation. EpCAM expression was positively correlated with activation of the mTOR and epithelial growth factor receptor (EGFR) signaling pathways. Furthermore, AMP-activated protein kinase (AMPK) was gradually de-activated in EpCAM-low PC-3 cells in the absence of serum.
CONCLUSIONS: EpCAM regulates the AMPK signaling pathway, essential for the response to growth factors characterized by EGF. LAT1, the amino acid transporter stabilized at the cellular membrane by EpCAM, is likely to be responsible for the difference in the susceptibility to EGF between EpCAM-high and EpCAM-low PC-3 cells.

Related: Prostate Cancer Signal Transduction EGFR Gefitinib (Iressa)

Yang Y, Fei F, Song Y, et al.
Polymorphisms of EpCAM gene and prognosis for non-small-cell lung cancer in Han Chinese.
Cancer Sci. 2014; 105(1):89-96 [PubMed] Related Publications
The epithelial cell adhesion molecule (EpCAM) is overexpressed in a wide variety of human cancers and is associated with patient prognosis, including those with lung cancer. However, the association of single nucleotide polymorphisms (SNPs) in the EpCAM gene with the prognosis for non-small-cell lung cancer (NSCLC) patients has never been investigated. We evaluated the association between two SNPs, rs1126497 and rs1421, in the EpCAM gene and clinical outcomes in a Chinese cohort of 506 NSCLC patients. The SNPs were genotyped using the Sequenom iPLEX genotyping system. Multivariate Cox proportional hazards model and Kaplan-Meier curves were used to assess the association of EpCAM gene genotypes with the prognosis of NSCLC. We found that the non-synonymous SNP rs1126497 was significantly associated with survival. Compared with the CC genotype, the CT+TT genotype was a risk factor for both death (hazard ratio, 1.40; 95% confidence interval [CI], 1.02-1.94; P = 0.040) and recurrence (hazard ratio, 1.34; 95% CI, 1.02-1.77; P = 0.039). However, the SNP rs1421 did not show any significant effect on patient prognosis. Instead, the AG+GG genotype in rs1421 was significantly associated with early T stages (T1/T2) when compared with the AA genotype (odds ratio for late stage = 0.65; 95% CI, 0.44-0.96, P = 0.029). Further stratified analysis showed notable modulating effects of clinical characteristics on the associations between variant genotypes of rs1126497 and NSCLC outcomes. In conclusion, our study indicated that the non-synonymous SNP rs1126497 may be a potential prognostic marker for NSCLC patients.

Related: Non-Small Cell Lung Cancer Lung Cancer

Saeed HM, Alanazi MS, Parine NR, et al.
Matrix metalloproteinase-2 (-1306 c>t) promoter polymorphism and risk of colorectal cancer in the Saudi population.
Asian Pac J Cancer Prev. 2013; 14(10):6025-30 [PubMed] Related Publications
BACKGROUND: Matrix metalloproteinase-2 (MMP-2) is an enzyme with proteolytic activity against matrix proteins, particularly basement membrane constituents. A single nucleotide polymorphism (SNP) at -1306, which disrupts a Sp1-type promoter site (CCACC box), results in strikingly lower promoter activity with the T allele. In the present study, we investigated whether this MMP-2 genetic polymorphism might be associated with susceptibility to colorectal cancer (CRC) in the Saudi population. We also analyzed MMP-2 gene expression level sin CRC patients and 4 different cancer cell lines.
MATERIALS AND METHODS: TaqMan allele discrimination assays and DNA sequencing techniques were used to investigate the C-1306T SNP in the MMP-2 gene of Saudi colorectal cancer patients and controls. The MMP-2 gene expression level was also determined in 12 colon cancer tissue samples collected from unrelated patients and histologically normal tissues distant from tumor margins.
RESULTS AND CONCLUSIONS: The MMP-2 C-1306T SNP in the promoter region was associated with CRC in our Saudi population and the MMP-2 gene expression level was found to be 10 times higher in CRC patients. The MMP-2 C-1306T SNP is significantly associated with CRC in the Saudi population and this finding suggested that MMP-2 variants might help predict CRC progression risk among Saudis. We propose that analysis of this gene polymorphism could assist in identification of patient subgroups at risk of a poor disease outcome.

Related: Colorectal (Bowel) Cancer MMP2

Shahneh FZ
Sensitive antibody-based CTCs detection from peripheral blood.
Hum Antibodies. 2013; 22(1-2):51-4 [PubMed] Related Publications
The detection of Circulating Tumor Cells (CTC) is a purpose in numerous oncology research fields. CTCs are disseminated from the original site from metastatic and primary tumors in the peripheral blood of breast, prostate, lung and colorectal cancer patients. Different characteristics of tumor cells have been applied to define enrichment methods through the differential expression of tumor-specific markers on the surface of the cells. Antibody-based affinity methods can provide the separation of CTCs via the expression of specific antigens on the surface of epithelial tumor cells or hematopoietic cells. Developments in CTC detection methods will improve a wide range of clinical applications, as well as the discovery of biomarkers to predict treatment responses and disease progression. In this mini-review, different CTCs detection approaches base on antibodies for enrichment of circulating tumor cells will be discussed and elucidated the methods for CTCs detection biomarkers on the current knowledge.

Related: Cancer Prevention and Risk Reduction PTPRC

Ahmad A, Maitah MY, Ginnebaugh KR, et al.
Inhibition of Hedgehog signaling sensitizes NSCLC cells to standard therapies through modulation of EMT-regulating miRNAs.
J Hematol Oncol. 2013; 6(1):77 [PubMed] Article available free on PMC after 23/05/2015 Related Publications
BACKGROUND: Epidermal growth factor receptor- tyrosine kinase inhibitors (EGFR-TKIs) benefit Non-small cell lung cancer (NSCLC) patients, and an EGFR-TKIi erlotinib, is approved for patients with recurrent NSCLC. However, resistance to erlotinib is a major clinical problem. Earlier we have demonstrated the role of Hedgehog (Hh) signaling in Epithelial-to-Mesenchymal transition (EMT) of NSCLC cells, leading to increased proliferation and invasion. Here, we investigated the role of Hh signaling in erlotinib resistance of TGF-β1-induced NSCLC cells that are reminiscent of EMT cells.
METHODS: Hh signaling was inhibited by specific siRNA and by GDC-0449, a small molecule antagonist of G protein coupled receptor smoothened in the Hh pathway. Not all NSCLC patients are likely to benefit from EGFR-TKIs and, therefore, cisplatin was used to further demonstrate a role of inhibition of Hh signaling in sensitization of resistant EMT cells. Specific pre- and anti-miRNA preparations were used to study the mechanistic involvement of miRNAs in drug resistance mechanism.
RESULTS: siRNA-mediated inhibition as well as pharmacological inhibition of Hh signaling abrogated resistance of NSCLC cells to erlotinib and cisplatin. It also resulted in re-sensitization of TGF-β1-induced A549 (A549M) cells as well the mesenchymal phenotypic H1299 cells to erlotinib and cisplatin treatment with concomitant up-regulation of cancer stem cell (CSC) markers (Sox2, Nanog and EpCAM) and down-regulation of miR-200 and let-7 family miRNAs. Ectopic up-regulation of miRNAs, especially miR-200b and let-7c, significantly diminished the erlotinib resistance of A549M cells. Inhibition of Hh signaling by GDC-0449 in EMT cells resulted in the attenuation of CSC markers and up-regulation of miR-200b and let-7c, leading to sensitization of EMT cells to drug treatment, thus, confirming a connection between Hh signaling, miRNAs and drug resistance.
CONCLUSIONS: We demonstrate that Hh pathway, through EMT-induction, leads to reduced sensitivity to EGFR-TKIs in NSCLCs. Therefore, targeting Hh pathway may lead to the reversal of EMT phenotype and improve the therapeutic efficacy of EGFR-TKIs in NSCLC patients.

Related: Non-Small Cell Lung Cancer Cisplatin Lung Cancer Signal Transduction EGFR Erlotinib (Tarceva)

Zhang P, Shi B, Gao H, et al.
An EpCAM/CD3 bispecific antibody efficiently eliminates hepatocellular carcinoma cells with limited galectin-1 expression.
Cancer Immunol Immunother. 2014; 63(2):121-32 [PubMed] Related Publications
There have been several studies suggesting that cancer stem cells (CSCs) contribute to the high rates of recurrence and resistance to therapies observed in hepatocellular carcinoma (HCC). Epithelial cell adhesion molecule (EpCAM) has been demonstrated to be a biomarker of CSCs and a potential therapeutic target in HCC. Here, we prepared two anti-EpCAM monoclonal antibodies (1H8 and 2F2) and an anti-EpCAM bispecific T cell engager (BiTE) 1H8/CD3, which was derived from 1H8, and used them to treat HCC in vitro and in vivo. The results demonstrated that all of the developed anti-EpCAM antibodies specifically bound to EpCAM. Neither anti-EpCAM monoclonal antibody had obvious anti-HCC activities in vitro or in vivo. However, anti-EpCAM BiTE 1H8/CD3 induced strong peripheral blood mononuclear cell-dependent cellular cytotoxicity in Huh-7 and Hep3B cells but not EpCAM-negative SK-Hep-1 cells. Notably, 1H8/CD3 completely inhibited the growth of Huh-7 and Hep3B xenografts in vivo. Treatment of the Huh-7 HCC xenografts with 1H8/CD3 significantly suppressed tumor proliferation and reduced the expression of most CSC biomarkers. Intriguingly, galectin-1 (Gal-1) overexpression inhibited 1H8/CD3-induced lymphocytotoxicity in HCCs while knockdown of Gal-1 increased the lymphocytotoxicity. Collectively, these results indicate that anti-EpCAM BiTE 1H8/CD3 is a promising therapeutic agent for HCC treatment. Gal-1 may contribute to the resistance of HCC cells to 1H8/CD3-induced lysis.

Related: Monoclonal Antibodies Liver Cancer

Sobrevals L, Mato-Berciano A, Urtasun N, et al.
uPAR-controlled oncolytic adenoviruses eliminate cancer stem cells in human pancreatic tumors.
Stem Cell Res. 2014; 12(1):1-10 [PubMed] Related Publications
Pancreatic tumors contain cancer stem cells highly resistant to chemotherapy. The identification of therapies that can eliminate this population of cells might provide with more effective treatments. In the current work we evaluated the potential of oncolytic adenoviruses to act against pancreatic cancer stem cells (PCSC). PCSC from two patient-derived xenograft models were isolated from orthotopic pancreatic tumors treated with saline, or with the chemotherapeutic agent gemcitabine. An enrichment in the number of PCSC expressing the cell surface marker CD133 and a marked enhancement on tumorsphere formation was observed in gemcitabine treated tumors. No significant increase in the CD44, CD24, and epithelial-specific antigen (ESA) positive cells was observed. Neoplastic sphere-forming cells were susceptible to adenoviral infection and exposure to oncolytic adenoviruses resulted in elevated cytotoxicity with both Adwt and the tumor specific AduPARE1A adenovirus. In vivo, intravenous administration of a single dose of AduPARE1A in human-derived pancreatic xenografts led to a remarkable anti-tumor effect. In contrast to gemcitabine AduPARE1A treatment did not result in PCSC enrichment. No enrichment on tumorspheres neither on the CD133(+) population was detected. Therefore our data provide evidences of the relevance of uPAR-controlled oncolytic adenoviruses for the elimination of pancreatic cancer stem cells.

Related: Cancer of the Pancreas Pancreatic Cancer Gemcitabine

Iliou MS, da Silva-Diz V, Carmona FJ, et al.
Impaired DICER1 function promotes stemness and metastasis in colon cancer.
Oncogene. 2014; 33(30):4003-15 [PubMed] Article available free on PMC after 23/05/2015 Related Publications
Disruption of microRNA (miRNA) expression patterns is now being recognized as a hallmark of human cancer. The causes of these altered profiles are diverse, and, among them, we found the existence of defects in the miRNA processing machinery. However, little is known about how these alterations affect the biology of the underlying tumors. Herein, we show that colorectal cancer cells with an impairment in DICER1, a major miRNA biogenesis gene, undergo enrichment of tumor stemness features and an epithelial-to-mesenchymal transition. These phenotypes are associated with the downregulation of miRNAs, such as miR-34a, miR-126 and those of the miR-200 family, that target critical coding genes in these pathways. Most importantly, DICER1 impairment also induces the acquisition of a greater capacity for tumor initiation and metastasis, two properties associated with cancer stem cells.

Related: DICER1

Duechler M, Peczek L, Zuk K, et al.
The heterogeneous immune microenvironment in breast cancer is affected by hypoxia-related genes.
Immunobiology. 2014; 219(2):158-65 [PubMed] Related Publications
The immune system constitutes an important first-line defence against malignant transformation. However, cancer mediated immunosuppression inactivates the mechanisms of host immune surveillance. Cancer cells shut down anti-cancer immunity through direct cell-cell interactions with leukocytes and through soluble factors, establishing an immunosuppressive environment for unimpeded cancer growth. The composition of the immunosuppressive microenvironment in breast tumours is not well documented. To address this question, selected immunosuppressive factors were analyzed in tumour specimens from 33 breast cancer patients after surgery. The mRNA expression of selected genes was quantified in fresh tumour samples. Tumour infiltrating leukocytes were characterized by flow cytometry to identify regulatory T cells, myeloid derived suppressor cells, and type 2 macrophages. Statistical analysis revealed several interesting correlations between the studied parameters and clinical features. Overall, a surprisingly high degree of heterogeneity in the composition of the immunosuppressive environment was found across all breast cancer samples which adds to the complexity of this disease. The influence of the hypoxia inducible factors (HIFs) on the immune microenvironment was also addressed. The level of HIFs correlated with hormone receptor status and the expression of several immunosuppressive molecules. Targeting HIFs might not only sensitize breast tumours for radiation and chemotherapies but also interfere with cancer immunosuppression.

Related: Breast Cancer HIF1A

Ryu JS, Lee JT, Lim MU, et al.
Plant-derived mAbs have effective anti-cancer activities by increasing ganglioside expression in colon cancers.
Biotechnol Lett. 2013; 35(12):2031-8 [PubMed] Related Publications
An epithelial cell adhesion molecule (EpCAM) was selectively expressed in human colorectal carcinoma. Treatment with plant-derived anti-EpCAM mAb (mAbP CO17-1A) and RAW264.7 cells inhibited cell growth in the human colorectal cancer cell line SW620. In SW620 treated with mAbP CO17-1A and RAW264.7 cells, expression of p53 and p21 increased, whereas the expression of G1 phase-related proteins, cyclin D1, CDK4, cyclin E, and CDK2, decreased, similar to mammalian-derived mAb (mAbM) CO17-1A. Similar to mAbM CO17-1A, treatment with mAbP CO17-1A and RAW264.7 cell decreased the expression of anti-apoptotic protein, Bcl-2, but the expression of pro-apoptotic proteins Bax, TNF-α, caspase-3, caspase-6, caspase-8 and caspase-9, increased. Cells treated with mAbP CO17-1A and RAW264.7 cells expressed metastasis-related gangliosides, GM1 and GD1a, similar to mAbM CO17-1A. These results suggest that mAbP CO17-1A is as effective on anti-cancer activity as mAbM CO17-1A.

Related: Monoclonal Antibodies Apoptosis

Hsu YT, Gu F, Huang YW, et al.
Promoter hypomethylation of EpCAM-regulated bone morphogenetic protein gene family in recurrent endometrial cancer.
Clin Cancer Res. 2013; 19(22):6272-85 [PubMed] Article available free on PMC after 23/05/2015 Related Publications
PURPOSE: Epigenetic regulation by promoter methylation plays a key role in tumorigenesis. Our goal was to investigate whether altered DNA methylation signatures associated with oncogenic signaling delineate biomarkers predictive of endometrial cancer recurrence.
EXPERIMENTAL DESIGN: Methyl-CpG-capture sequencing was used for global screening of aberrant DNA methylation in our endometrial cancer cohort, followed by validation in an independent The Cancer Genome Atlas (TCGA) cohort. Bioinformatics as well as functional analyses in vitro, using RNA interference (RNAi) knockdown, were performed to examine regulatory mechanisms of candidate gene expression and contribution to aggressive phenotype, such as epithelial-mesenchymal transition (EMT).
RESULTS: We identified 2,302 hypermethylated loci in endometrial tumors compared with control samples. Bone morphogenetic protein (BMP) family genes, including BMP1, 2, 3, 4, and 7, were among the frequently hypermethylated loci. Interestingly, BMP2, 3, 4, and 7 were less methylated in primary tumors with subsequent recurrence and in patients with shorter disease-free interval compared with nonrecurrent tumors, which was validated and associated with poor survival in the TCGA cohort (BMP4, P = 0.009; BMP7, P = 0.007). Stimulation of endometrial cancer cells with epidermal growth factor (EGF) induced EMT and transcriptional activation of these genes, which was mediated by the epithelial cell adhesion molecule (EpCAM). EGF signaling was implicated in maintaining the promoters of candidate BMP genes in an active chromatin configuration and thus subject to transcriptional activation.
CONCLUSIONS: Hypomethylation signatures of candidate BMP genes associated with EpCAM-mediated expression present putative biomarkers predictive of poor survival in endometrial cancer.

Related: Endometrial (Uterus) Cancer Endometrial Cancer

Ni J, Cozzi P, Hao J, et al.
Epithelial cell adhesion molecule (EpCAM) is associated with prostate cancer metastasis and chemo/radioresistance via the PI3K/Akt/mTOR signaling pathway.
Int J Biochem Cell Biol. 2013; 45(12):2736-48 [PubMed] Related Publications
Prostate cancer (CaP) is the second leading malignancy in men. The role of epithelial cell adhesion molecule (EpCAM), also known as CD326, in CaP progression and therapeutic resistance is still uncertain. Here, we aimed to investigate the roles of EpCAM in CaP metastasis and chemo/radioresistance. Expression of EpCAM in CaP cell lines and human CaP tissues was assessed using immunofluorescence and immunohistochemistry, respectively. EpCAM was knocked down (KD) in PC-3, DU145 and LNCaP-C4-2B cells using small interfering RNA (siRNA), and KD results were confirmed by confocal microscope, Western blotting and quantitative real time polymerase chain reaction (qRT-PCR). Cell growth was evaluated by proliferation and colony formation assays. The invasive potential was assessed using a matrigel chamber assay. Tumorigenesis potential was measured by a sphere formation assay. Chemo-/radiosensitivity were measured using a colony formation assay. Over-expression of EpCAM was found in primary CaP tissues and lymph node metastases including cancer cells and surrounding stromal cells. KD of EpCAM suppressed CaP proliferation and invasive ability, reduced sphere formation, enhanced chemo-/radiosensitivity, and down-regulated E-cadherin, p-Akt, p-mTOR, p-4EBP1 and p-S6K expression in CaP cells. Our findings suggest that EpCAM plays an important role in CaP proliferation, invasion, metastasis and chemo-/radioresistance associated with the activation of the PI3K/Akt/mTOR signaling pathway and is a novel therapeutic target to sensitize CaP cells to chemo-/radiotherapy.

Related: AKT1 Signal Transduction

Paniz Mondolfi AE, Jour G, Johnson M, et al.
Primary cutaneous carcinosarcoma: insights into its clonal origin and mutational pattern expression analysis through next-generation sequencing.
Hum Pathol. 2013; 44(12):2853-60 [PubMed] Related Publications
Primary cutaneous carcinosarcoma is a rare biphenotypic neoplasm exhibiting both epithelial and sarcomatous elements. Even though its origin and biological aspects remain poorly understood, it has been postulated that this tumor may arise from progenitor cells, which subsequently differentiate into distinct tumor components. We have investigated the histological and immunohistochemical staining patterns of a cutaneous carcinosarcoma case, as well as its ultrastructural aspects. In addition, sarcomatous and epithelial tumor components were separated by laser capture microdissection and subjected to targeted, high-depth, next-generation sequencing of a 46-cancer gene panel to asses the gene mutational pattern amongst both components. There were transitional cells at the epithelial/mesenchymal transition that labeled with putative progenitor cell markers (K19, c-kit, CD34 and Bcl-2). There was shared reactivity to antibodies directed against the progenitor cell marker EpCAM (epithelial cell adhesion molecule) in both components. Ultrastructurally, individual cells were demonstrated to have overlapping features of epithelial and mesenchymal differentiation. The mutational analysis revealed point mutations in exon 5 of TP53, which were identical in both the epithelial and sarcomatous components, and which were concordant with p53 expression at a tissue level. The aforementioned histological, ultrastructural, immunohistochemical and mutational pattern is strongly suggestive of a common clonal origin to the distinct elements of this tumor.

Related: Skin Cancer

Zhu WF, Li J, Yu LC, et al.
Prognostic value of EpCAM/MUC1 mRNA-positive cells in non-small cell lung cancer patients.
Tumour Biol. 2014; 35(2):1211-9 [PubMed] Related Publications
The aim of this study was to assess the prognostic value of EpCAM/MUC1 mRNA-positive circulating tumor cells (CTCs) in patients with non-small cell lung cancer (NSCLC). The presence of EpCAM/MUC1 mRNA-positive CTCs was evaluated in 74 NSCLC patients before the initiation of any therapy, from which 61 patients with surgical resection of tumor were also evaluable for EpCAM/MUC1 mRNA-positive CTC analysis after surgery, by quantitative real-time PCR assay. Sixty patients with benign lung disease (BLD) entered this study as controls. The results showed that blood levels of EpCAM and MUC1 mRNA in NSCLC patients before and after surgery were significantly higher than those in BLD patients (P = 0.001 and P = 0.015, respectively, for EpCAM; P = 0.003 and P = 0.026, respectively, for MUC1), and the levels of the two gene mRNA in NSCLC patients significantly decreased after surgery (P = 0.025 and P = 0.033, respectively). Disease recurrence significantly increased in NSCLC patients with EpCAM/MUC1 mRNA-positive CTC preoperation and postoperation (P = 0.004 and P = 0.001, respectively). Disease-free survival and overall survival significantly reduced in patients with EpCAM/MUC1 mRNA-positive CTC preoperation and postoperation (P = 0.012 and P = 0.002, respectively, for preoperation; both P < 0.001 for postoperation). Multivariate analysis demonstrated that the presence of EpCAM/MUC1 mRNA-positive CTCs before and after surgery was an independent factor associated with disease recurrence. In conclusion, the detection of EpCAM/MUC1 mRNA-positive CTCs in the blood before and after surgery is useful for predicting a poor prognosis in NSCLC patients who undergo curative surgery.

Related: Non-Small Cell Lung Cancer MUC1 gene

Sollier E, Go DE, Che J, et al.
Size-selective collection of circulating tumor cells using Vortex technology.
Lab Chip. 2014; 14(1):63-77 [PubMed] Related Publications
A blood-based, low cost alternative to radiation intensive CT and PET imaging is critically needed for cancer prognosis and management of its treatment. "Liquid biopsies" of circulating tumor cells (CTCs) from a relatively non-invasive blood draw are particularly ideal, as they can be repeated regularly to provide up to date molecular information about the cancer, which would also open up key opportunities for personalized therapies. Beyond solely diagnostic applications, CTCs are also a subject of interest for drug development and cancer research. In this paper, we adapt a technology previously introduced, combining the use of micro-scale vortices and inertial focusing, specifically for the high-purity extraction of CTCs from blood samples. First, we systematically varied parameters including channel dimensions and flow rates to arrive at an optimal device for maximum trapping efficiency and purity. Second, we validated the final device for capture of cancer cell lines in blood, considering several factors, including the effect of blood dilution, red blood cell lysis and cell deformability, while demonstrating cell viability and independence on EpCAM expression. Finally, as a proof-of-concept, CTCs were successfully extracted and enumerated from the blood of patients with breast (N = 4, 25-51 CTCs per 7.5 mL) and lung cancer (N = 8, 23-317 CTCs per 7.5 mL). Importantly, samples were highly pure with limited leukocyte contamination (purity 57-94%). This Vortex approach offers significant advantages over existing technologies, especially in terms of processing time (20 min for 7.5 mL of whole blood), sample concentration (collecting cells in a small volume down to 300 μL), applicability to various cancer types, cell integrity and purity. We anticipate that its simplicity will aid widespread adoption by clinicians and biologists who desire to not only enumerate CTCs, but also uncover new CTC biology, such as unique gene mutations, vesicle secretion and roles in metastatic processes.

Related: Breast Cancer Lung Cancer


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Cite this page: Cotterill SJ. EPCAM, Cancer Genetics Web: http://www.cancerindex.org/geneweb/M4S1.htm Accessed: date

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