Gene Summary

Gene:KRT7; keratin 7
Aliases: K7, CK7, SCL, K2C7
Summary:The protein encoded by this gene is a member of the keratin gene family. The type II cytokeratins consist of basic or neutral proteins which are arranged in pairs of heterotypic keratin chains coexpressed during differentiation of simple and stratified epithelial tissues. This type II cytokeratin is specifically expressed in the simple epithelia lining the cavities of the internal organs and in the gland ducts and blood vessels. The genes encoding the type II cytokeratins are clustered in a region of chromosome 12q12-q13. Alternative splicing may result in several transcript variants; however, not all variants have been fully described. [provided by RefSeq, Jul 2008]
Databases:OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:keratin, type II cytoskeletal 7
Source:NCBIAccessed: 31 August, 2019


What does this gene/protein do?
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Pathways:What pathways are this gene/protein implicaed in?
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Cancer Overview

Research Indicators

Publications Per Year (1994-2019)
Graph generated 31 August 2019 using data from PubMed using criteria.

Literature Analysis

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Tag cloud generated 31 August, 2019 using data from PubMed, MeSH and CancerIndex

Latest Publications: KRT7 (cancer-related)

Shao K, Wang Y, Xue Q, et al.
Clinicopathological features and prognosis of ciliated muconodular papillary tumor.
J Cardiothorac Surg. 2019; 14(1):143 [PubMed] Free Access to Full Article Related Publications
BACKGROUNDS: The pulmonary ciliated muconodular papillary tumor (CMPT) is a very rare tumor with only several case reports in published literatures, and its clinicopathological features, standard treatment methods and prognosis has not been well defined.
METHODS: Two cases of CMPT diagnosed and treated in our hospital and 39 cases reported in the published literature were analyzed retrospectively.
RESULTS: The cohort of 41 CMPT patients comprised of 20 males and 21 females, aged 9-84 years. The diameter of the primary tumor was 0.3-4.5 cm. Most of these lesions were subsolid nodules, as observed on computed tomography and easily misdiagnosed as early lung adenocarcinoma. Tumors of 26 patients were stained by immunohistochemistry method, which revealed that CK7, CEA, and TTF-1 were positive and CK20 was negative in most patients. The results of gene alternation demonstrated mutations in EGFR, KRAS, and BRAF and ALK rearrangements in CMPT. All the patients underwent surgical treatment and did not receive postoperative adjuvant therapy. The follow-up duration was 0-120 months, and no case of tumor recurrence was found until the final follow-up.
CONCLUSIONS: The incidence of CMPT was low and rate of image misdiagnosis high. Immunohistochemistry is helpful for accurate diagnosis of CMPT. Sub-lobectomy may be proper and adjuvant treatment should be avoided since the disease is now prone to benign lesions. Furthermore, since the biological behavior of this tumor is not yet fully elucidated, additional case data are essential for accurate conclusions.

Huang YL, Chang YL, Chen KC, Wu CT
Mixed squamous cell and glandular papilloma of the lung: A case report of a novel mutation in the BRAF gene and coexistent HPV infection, possible relationship to ciliated muconodular papillary tumor.
Pathol Int. 2019; 69(2):104-109 [PubMed] Related Publications
Mixed squamous cell and glandular papilloma (mixed papilloma) is a very rare tumor, with fewer than 25 cases having been reported in the literature. Although a scattering of cases of p16

Liao X, Houldsworth J, Luo J, et al.
Polypoid Undifferentiated Carcinoma With Osteoclast-like Giant Cells Arising in the Distal Common Bile Duct: A Rare Case Report.
Anticancer Res. 2019; 39(1):437-441 [PubMed] Related Publications
BACKGROUND: Undifferentiated carcinoma with osteoclast-like giant cells (UC-OGC) in distal common bile duct (CBD) is a rare entity.
CASE REPORT: This case report describes a 45-year-old male with a history of a choledochal cyst status post partial excision and cholecystectomy who presented with a mass in the remaining distal/intrapancreatic common bile duct. It was initially mistaken for post-surgery hematoma; however, the rapid growth raised concern for malignancy, and prompted a pancreaticoduodenectomy (Whipple) procedure. Macroscopic examination revealed a 5.5 cm polypoid mass grossly confined in the lumen of the distal CBD. Histology was consistent with UC-OGC, with minimal invasion into the polyp stalk and adjacent CBD wall. Immunohistochemistry demonstrated co-expression of CK7 and p40, normal/wild-type p53, and retained SMAD4 expression in tumor cells. Next-generation sequencing detected mutations at p.Q61H (c.183A>C) of KRAS and p.E545K (c.1633G>A) of PIK3CA, keeping in line with similarity to conventional cholangiocarcinoma. The patient remained disease-free after two years of follow-up without chemotherapy.
CONCLUSION: To our knowledge, this is the first case report of UC-OGC presented as a polypoid mass in the distal CBD. It highlights the complex dynamism and controversial pathogenesis of this unique entity, which should be made aware to avoid diagnostic pitfalls.

Alaghehbandan R, Ulamec M, Martinek P, et al.
Papillary pattern in clear cell renal cell carcinoma: Clinicopathologic, morphologic, immunohistochemical and molecular genetic analysis of 23 cases.
Ann Diagn Pathol. 2019; 38:80-86 [PubMed] Related Publications
Clear cell renal cell carcinoma (ccRCC), the most common histologic subtype of RCCs, demonstrates a wide spectrum of morphologic features (i.e., low-grade spindle cell, syncytial giant cells, and mucin-producing cells). However, papillary growth pattern in ccRCCs is rather a rare finding, which can present challenges in differential diagnostic work up. The aim of this study was to investigate ccRCCs with predominant papillary features from morphologic, immunohistochemical and molecular genetic perspectives. 23 clear cell renal cell carcinomas with papillary architecture were selected. Tumors were evaluated morphologically, immunohistochemically, and molecularly by next-generation sequencing (NGS). The diagnosis of MiT family translocation RCC was excluded by TFE3 immunohistochemistry. Mean age of patients was 65.2 years (range 42-81 years), and 19/23 were male. Tumor size ranged from 1.6 to 12.8 cm (median 6.5 cm). At a median follow-up of 2.5 years (range 1.5-9 years), 2 patients (8.7%) died of disease, 2 developed metastasis. Areas of papillary pattern accounted for approximately 40-100% of the tumor. CK7 was negative in non-papillary areas in majority of cases (20/23, 87%), and was only focally positive in 3/23 cases (13%). In papillary areas, AMACR was positive/focally positive in 17/23 (73.9%) cases and in the non-papillary areas it was positive/focally positive in 22/23 (95.6%) cases. CAIX was mainly negative in both non-papillary and papillary areas (15/23 [65%] and 16/23 [69.5%], respectively). Molecular analysis of 15 analyzable cases revealed the most frequently mutated gene to be VHL (in 9 cases), followed by PRBM1 (in 2 cases) and 29 other different mutations in various genes. Papillary growth pattern in ccRCC is not an uncommon situation. Papillary RCC with clear cells and MiT family (TFE3) translocation RCCs are the major differential diagnostic considerations in such scenarios. Our NGS molecular analysis supported classifying such tumors as a morphologic variant of ccRCC.

Wu X, Xiao Y, Yan W, et al.
The human oncogene SCL/TAL1 interrupting locus (STIL) promotes tumor growth through MAPK/ERK, PI3K/Akt and AMPK pathways in prostate cancer.
Gene. 2019; 686:220-227 [PubMed] Related Publications
The morbidity and mortality of prostate cancer (PCa) in China have increased obviously, which became the second leading cause of death in men with cancer. Hedgehog (Hh) signaling pathway is a key signaling pathway involved in the prostate cancer progression. The human oncogene SCL/TAL1 interrupting locus (STIL) can modulate the Hh signaling pathway, but its function in PCa has not been reported. Here, we showed that STIL was increased in high grade prostate cancer tissue. Knockdown of STIL in prostate cancer cells PC-3 and DU 145 significantly decreased the proliferation of cells and induced cellular apoptosis through casepase3/7 mediated pathway. Moreover, the colony formation ability was also inhibited when knockdown of STIL by lentivirus-mediated shRNA. Furthermore, the cellular signaling antibody array analysis revealed which signaling pathway was affected when silencing STIL. Altogether, we found that STIL could affect MAPK/ERK, PI3K/Akt and AMPK signaling pathways, thus promoting cellular proliferation, colony formation and suppressing cellular apoptosis in prostate cancer.

Jester R, Znoyko I, Garnovskaya M, et al.
Expression of renal cell markers and detection of 3p loss links endolymphatic sac tumor to renal cell carcinoma and warrants careful evaluation to avoid diagnostic pitfalls.
Acta Neuropathol Commun. 2018; 6(1):107 [PubMed] Free Access to Full Article Related Publications
Endolymphatic sac tumor (ELST) is a rare neoplasm arising in the temporal petrous region thought to originate from endolymphatic sac epithelium. It may arise sporadically or in association with Von-Hippel-Lindau syndrome (VHL). The ELST prevalence in VHL ranges from 3 to 16% and may be the initial presentation of the disease. Onset is usually in the 3rd to 5th decade with hearing loss and an indolent course. ELSTs present as locally destructive lesions with characteristic computed tomography imaging features. Histologically, they show papillary, cystic or glandular architectures. Immunohistochemically, they express keratin, EMA, and variably S100 and GFAP. Currently it is recommended that, given its rarity, ELST needs to be differentiated from other entities with similar morphologic patterns, particularly other VHL-associated neoplasms such as metastatic clear cell renal cell carcinoma (ccRCC). Nineteen ELST cases were studied. Immunohistochemistry (18/19) and single nucleotide polymorphism microarray testing was performed (12/19). Comparison with the immunophenotype and copy number profile in RCC is discussed. Patients presented with characteristic bone destructive lesions in the petrous temporal bones. Pathology of tumors showed characteristic ELST morphology with immunoexpression of CK7, GFAP, S100, PAX-8, PAX-2, CA-9 in the tumor cells. Immunostaines for RCC, CD10, CK20, chromogranin A, synaptophysin, TTF-1, thyroglobulin, and transthyretin were negative in the tumor cells. Molecular testing showed loss of 3p and 9q in 66% (8/12) and 58% (7/12) cases, respectively. Immunoreactivity for renal markers in ELST is an important diagnostic caveat and has not been previously reported. In fact, renal markers are currently recommended in order to rule out metastatic RCC although PAX gene complex and CA-9 have been implicated in the development of the inner ear. Importantly copy number assessment of ELST has not been previously reported. Loss of 3p (including the VHL locus) in ELST suggests similar mechanistic origins as ccRCC.

Wang P, Magdolen V, Seidl C, et al.
Kallikrein-related peptidases 4, 5, 6 and 7 regulate tumour-associated factors in serous ovarian cancer.
Br J Cancer. 2018; 119(7):1-9 [PubMed] Article available free on PMC after 02/10/2019 Related Publications
BACKGROUND: Tissue kallikrein-related peptidases 4, 5, 6 and 7 (KLK4-7) strongly increase the malignancy of ovarian cancer cells. Deciphering their downstream effectors, we aimed at finding new potential prognostic biomarkers and treatment targets for ovarian cancer patients. KLK4-7-transfected (OV-KLK4-7) and vector-control OV-MZ-6 (OV-VC) ovarian cancer cells were established to select differentially regulated factors.
METHODS: With three independent approaches, PCR arrays, genome-wide microarray and proteome analyses, we identified 10 candidates (MSN, KRT19, COL5A2, COL1A2, BMP5, F10, KRT7, JUNB, BMP4, MMP1). To determine differential protein expression, we performed western blot analyses, immunofluorescence and immunohistochemistry for four candidates (MSN, KRT19, KRT7, JUNB) in cells, tumour xenograft and patient-derived tissues.
RESULTS: We demonstrated that KLK4-7 clearly regulates expression of MSN, KRT19, KRT7 and JUNB at the mRNA and protein levels in ovarian cancer cells and tissues. Protein expression of the top-upregulated effectors, MSN and KRT19, was investigated by immunohistochemistry in patients afflicted with serous ovarian cancer and related to KLK4-7 immunoexpression. Significant positive associations were found for KRT19/KLK4, KRT19/KLK5 and MSN/KLK7.
CONCLUSION: These findings imply that KLK4-7 exert key modulatory effects on other cancer-related genes and proteins in ovarian cancer. These downstream effectors of KLK4-7, MSN and KRT19 may represent important therapeutic targets in serous ovarian cancer.

Rahman FU, Bhatti MZ, Ali A, et al.
Dimetallic Ru(II) arene complexes appended on bis-salicylaldimine induce cancer cell death and suppress invasion via p53-dependent signaling.
Eur J Med Chem. 2018; 157:1480-1490 [PubMed] Related Publications
A series of bis-salicylaldimine ligands bearing two ON-donor functions were reacted with dichloro(p-cymene)ruthenium(II) dimer in the presence of base (NaOAc) and a series of four dimetallic Ru(II) arene complexes (Ru(p-cymene))

Lin J, Cao Y, Yu L, Lin L
Non-α-fetoprotein-producing adrenal hepatoid adenocarcinoma: A case report and literature review.
Medicine (Baltimore). 2018; 97(39):e12336 [PubMed] Article available free on PMC after 02/10/2019 Related Publications
RATIONALE: Adrenal hepatoid adenocarcinoma typically secretes alpha-fetoprotein (AFP). Here, we report a case of non-AFP-producing adrenal hepatoid adenocarcinoma. Next-generation sequencing (NGS) was conducted to identify gene mutations.
PATIENT CONCERNS: A 64-year-old man presented with mild back pain and unexplained weight loss for 3 months.
DIAGNOSES: Contrast-enhanced magnetic resonance imaging (MRI) showed a mass (9.9 × 9.7 × 9.1 mm) above the upper pole of the left kidney. The left renal artery and vein were compressed. The tumor was positive for CK8/18, CK19, CK7, hepatocyte marker (Hepatocyte), and Hep Par 1, but negative for AFP. Plasma AFP was 2.75 ng/mL (normal range: 0-7 ng/mL). NGS revealed mutations of the following genes: ATM, CDKN2A, EGFR, STK11, TP53, BIM, and MLH1. A diagnosis of adrenal hepatoid adenocarcinoma was established.
INTERVENTIONS: The treatment included 4 cycles of the mFOLFOX6 regimen (oxaliplatin, leucovorin, and fluorouracil), transcatheter arterial chemoembolization, and apatinib.
OUTCOMES: The patient died 9 months after the diagnosis.
LESSONS: This case highlights the importance of thorough clinical, radiological, and immunohistochemical investigation for suspected adrenal hepatoid adenocarcinoma. Metastasis from other primary tumors should be ruled out. Furthermore, AFP is not necessarily elevated in adrenal hepatoid adenocarcinoma. NGS could be helpful in establishing the diagnosis and selecting treatments.

Meng FT, Huang M, Shao F, Huang Q
Upregulated FFAR4 correlates with the epithelial-mesenchymal transition and an unfavorable prognosis in human cholangiocarcinoma.
Cancer Biomark. 2018; 23(3):353-361 [PubMed] Related Publications
BACKGROUND: Free fatty acid receptor 4 (FFAR4) is associated with the epithelial mesenchymal transition (EMT) and is involved in the progression of several types of cancer. However, the role of FFAR4 in cholangiocarcinoma (CCA) remains unclear.
OBJECTIVE: The present study evaluated the diagnosis and prognosis of CCA using FFAR4 as a biomarker.
METHODS: Immunohistochemistry was employed to detect expression of FFAR4 in 98 samples of CCA tissues and adjacent tissues. In addition, expression of E-cadherin, vimentin, Snail-1, CK7 and CK19 in the 98 samples of CCA tissues was detected, and relationships with FFAR4 were analyzed. Correlation between FFAR4 and clinical pathological factors and prognosis was also analyzed.
RESULTS: FFAR4 was highly expressed in 72.4% (71/98) of CCA tissues and 29.6% (29/98) of adjacent tissues, with a statistically significant difference between the two tissue types (P< 0.05). A negative correlation between high expression FFAR4 and E-cadherin expression in CCA tissues was also observed (r=-0.445, P< 0.001), and high expression of FFAR4 was positively correlated with vimentin (r= 0.354, P< 0.001), Snail-1(r= 0.496, P< 0.001), CK7(r= 0.494, P< 0.001) and CK19 (r= 0.532, P< 0.001). Moreover, the degree of FFAR4 expression was associated with aggressive clinicopathological characteristics, such as histological grade, perineural invasion (PNI), lymph node metastasis (LNM), advanced TNM stage and preoperative serum CA19-9 level (P< 0.05). In terms of prognosis, CCA patients with high FFAR4 expression showed shorter disease-free survival (DFS) (P< 0.05) and overall survival (OS) (P< 0.05) than did patients with low FFAR4 expression.
CONCLUSIONS: FFAR4 overexpression may mediate the process of CCA EMT. In addition, FFAR4 is promising as a new diagnostic molecule and therapeutic target for CCA.

Xia F, Ling W, Zhang J, et al.
Primary poorly differentiated lacrimal gland adenocarcinoma in left ocular region: A rare case report.
Medicine (Baltimore). 2018; 97(37):e12198 [PubMed] Article available free on PMC after 02/10/2019 Related Publications
RATIONALE: Primary poorly differentiated lacrimal gland adenocarcinoma in the orbital region is an extremely rare type of neoplasm with only 1 related case in the literature. Its high grade of malignancy makes the timely data reported necessary. Hence, we present an extremely rare disease with biopsy results and recommendations on clinical treatment in an elderly male with Chinese descent.
PATIENT CONCERNS: A 66-year-old Chinese man presented with swelling in the left ocular region and eyeball proptosis. On physical examination, the patient had redness, tenderness, and swelling of the left eye. A surgical incision was noted on the left orbital region. Left eye movements were restricted.
DIAGNOSES: Immunohistochemical examination revealed pan-cytokeratin (PCK, +), p63 (partial, +), cytokeratin 7 (CK7, +), cytokeratin 14 (CK14, +), epithelial membrane antigen (EMA, +), protein expressed by erythroblast transformation-specific related gene (ERG, -), S-100 (, -), Epstein-Barr virus-encoded small RNA (EBER, -), smooth muscle actin (SMA, -), and Ki-67 (with a proliferation index approximately 40%). After carefully reviewed the manifestations, imaging findings, and immunohistochemical evidences, a diagnosis of poorly differentiated adenocarcinoma of lacrimal gland was made.
INTERVENTION: Based on the gene sequencing results, we started the patient with an intensive PF chemotherapy including a combination of cisplatine, fluorouracil, and epirubicin. Two months later, radiotherapy was introduced to the therapy regimen.
OUTCOMES: The patient responded well to the treatment without severe adverse events. MRI scan showed remarkable remission.
LESSONS: This rare case report will help raise the awareness of high grade lacrimal gland cancer, and subsequently aid the diagnosis in future cases. Positive immunohistochemical markers of CK7, CK14, EMA, p63, and high proliferation index of Ki-67 can help establishing a diagnosis, and cisplatine-fluorouracil program is proved feasible. We share the difficulties we have encountered, hoping to improve patient care in the future.

Sarlos DP, Peterfi L, Szanto A, Kovacs G
Shift of Keratin Expression Profile in End-stage Kidney Increases the Risk of Tumor Development.
Anticancer Res. 2018; 38(9):5217-5222 [PubMed] Related Publications
BACKGROUND/AIM: Pre-neoplastic lesions and renal cell tumors of distinct pheno- and genotypes occur frequently in end-stage kidneys. The aim of this study was to investigate the role of KRT7 and KRT19 in this process, the expression of which was previously detected by Affymetrix GeneChip analysis.
PATIENTS AND METHODS: Twelve end-stage kidneys were analyzed to find pre-neoplastic lesions and tumors and expression of KRT7 and KRT19 was examined by immunohistochemistry.
RESULTS: A total of 17 tumors, 149 pre-neoplastic lesions, 179 simple or proliferative cysts >2 mm were identified. Diffuse expression of KRT7 and KRT19 was seen in all end-stage kidneys as well as in the vast majority of cysts, pre-neoplastic lesions and tumors.
CONCLUSION: Our data indicates that de novo expression of KRT7 and KRT19 resulting in altered plasticity and stem cell characteristics of epithelial cells might be a crucial factor in increasing the risk of tumor development in end-stage kidneys.

Tan TK, Zhang C, Sanda T
Oncogenic transcriptional program driven by TAL1 in T-cell acute lymphoblastic leukemia.
Int J Hematol. 2019; 109(1):5-17 [PubMed] Related Publications
TAL1/SCL is a prime example of an oncogenic transcription factor that is abnormally expressed in acute leukemia due to the replacement of regulator elements. This gene has also been recognized as an essential regulator of hematopoiesis. TAL1 expression is strictly regulated in a lineage- and stage-specific manner. Such precise control is crucial for the switching of the transcriptional program. The misexpression of TAL1 in immature thymocytes leads to a widespread series of orchestrated downstream events that affect several different cellular machineries, resulting in a lethal consequence, namely T-cell acute lymphoblastic leukemia (T-ALL). In this article, we will discuss the transcriptional regulatory network and downstream target genes, including protein-coding genes and non-coding RNAs, controlled by TAL1 in normal hematopoiesis and T-cell leukemogenesis.

Michalova K, Steiner P, Alaghehbandan R, et al.
Papillary renal cell carcinoma with cytologic and molecular genetic features overlapping with renal oncocytoma: Analysis of 10 cases.
Ann Diagn Pathol. 2018; 35:1-6 [PubMed] Related Publications
BACKGROUND: We present a series of papillary renal cell carcinomas (PRCC) reminiscent of so-called "oncocytic variant of papillary renal cell carcinoma" (OPRCC), included in the 2016 WHO classification as a potential type 3 PRCC. OPRCC is a poorly understood entity, cytologically characterized by oncocytic cells with non-overlapping low grade nuclei. OPRCC is not genotypically distinct and the studies concerning this variant have shown an inconsistent genetic profile. The tumors presented herein demonstrated predominantly papillary/tubulopapillary architecture and differed from OPRCC by pseudostratification and grade 2-3 nuclei (Fuhrman/ISUP). Because there is a morphologic overlap between renal oncocytoma (RO) and PRCC in the cases included in this study, the most frequently affected chromosomes in RO and PRCC were analyzed.
MATERIALS AND METHODS: 147 PRCC composed of oncocytic cells were retrieved from our registry in order to select a group of morphologically uniform tumors. 10 cases with predominantly papillary, tubulopapillary or solid architectural patterns were identified. For immunohistochemical analysis, the following antibodies were used: vimentin, antimitochondrial antigene (MIA), AMACR, PAX8, CK7, CK20, AE1-3, CAM5.2, OSCAR, Cathepsin K, HMB45, SDHB, CD10, and CD117. Enumeration changes of locus 1p36, chromosomes 7, 14, 17, X, Y and rearrangement of CCND1 were examined by FISH. For further study, only tumors showing karyotype similar to that of RO were selected. The tumors exhibiting either trisomy of chromosomes 7, 17 or gain of Y, thus abnormalities characteristic for PRCC, were excluded.
RESULTS: There were 5 males and 5 females, with patient age ranging from 56 to 79 years (mean 66.8 years). The tumor size ranged from 2 to 10 cm (mean 5.1 cm). Follow-up was available for 8/10 patients (mean 5.2 years); one patient died of the disease, while 7 of 8 are alive and well. Immunohistochemically, all cases were reactive for AMACR, vimentin, PAX8, OSCAR, CAM5.2, and MIA. SDHB was retained in all cases. 9/10 cases were positive for CD10, 7/10 cases reacted with CK7, 4/10 with Cathepsin K, and 2/10 with AE1-3. None of the cases were positive for CD117, HMB45 and CK20. All 10 cases were analyzable by FISH and showed chromosomal abnormalities similar to that usually seen in RO (i.e. loss of 1p36 gene loci, loss of chromosome Y, rearrangement of CCND1 and numerical changes of chromosome 14).
CONCLUSIONS: We analyzed a series of renal tumors combining the features of PRCC/OPRCC and RO, that included pseudostratification and mostly high grade oncocytic cells lining papillary/tubulopapillary structures, karyotype characterized by loss of 1p36, loss of chromosome Y, rearrangement of CCND1 gene and numerical changes of chromosome 14. Despite the chromosomal numerical abnormalities typical of RO, we classified these tumors as part of the spectrum of PRCC because of their predominant papillary/tubulopapillary architecture, immunoprofile that included reactivity for AMACR, vimentin and lack of reactivity for CD117, all of which is incompatible with the diagnosis of RO. This study expands the morphological spectrum of PRCC by adding a cohort of diagnostically challenging cases, which may be potentially aggressive.

Park CK, Malinowski DP, Cho NH
Diagnostic algorithm for determining primary tumor sites using peritoneal fluid.
PLoS One. 2018; 13(7):e0199715 [PubMed] Article available free on PMC after 02/10/2019 Related Publications
This study was conducted to develop a novel algorithm for determining the origin of tumors by combining analysis of cluster patterns with immunocytochemistry (ICC) for markers in cells from fine-needle aspirates of ascites. We used LBC, based on SurePathTM (BD Diagnostics) technology, to screen 96 peritoneal fluid samples from patients with known malignancies and from 10 control patients with cirrhosis. Following dual ICC staining for cytokeratin 7 (CK7) and paired box gene 8 (PAX8), we developed an algorithm using immunoreactivity and three-dimensional (3D) cluster patterns to correlate staining and 3D cluster patterns with common primary origins that included stomach, ovarian, pancreatobiliary tract, colon, lung, and breast cancers. With the application of an automatic digitalized image analyzer, competence performance was analyzed using receiver operating characteristics (ROC) curve analysis. CK7 and PAX8 staining and 3D cluster patterns were used to differentiate primary origins. Samples from patients with stomach cancer were no 3D cluster /CK7+/PAX8- with area under the curve (AUC) of 0.8699 in ROC curve analysis. Samples from ovarian cancer patients were large 3D cluster/CK7+/PAX8+ with AUC of 0.9812. Samples from pancreatobiliary tract cancer patients were small 3D cluster/CK7+/PAX8- with AUC of 0.8772. The remaining cancer samples, including breast, lung and colon cancer samples, had similar patterns of large 3D clusters/CK7+/PAX8- with AUC of 0.882, especially for lung cancer. SurePathTM technology, using 3D cluster patterns and dual ICC for CK7 and PAX8 in peritoneal fluid samples, can provide important information for determining specific primary origins in cases of unknown primary carcinoma.

Gustafsson BM, Mattsson K, Bogdanovic G, et al.
Origins of STIL-TAL1 fusion genes in children who later developed paediatric T-cell acute lymphoblastic leukaemia: An investigation of neonatal blood spots.
Pediatr Blood Cancer. 2018; 65(11):e27310 [PubMed] Related Publications
SCL/TAL1 interrupting locus (STIL)-T-cell acute leukaemia (TAL1) fusion genes are present in approximately 11-27% of children with paediatric T-cell acute lymphoblastic leukaemia (T-ALL), but the developmental timing of the rearrangement is still unknown. To investigate whether the fusion gene can be detected in neonatal blood spots (NBSs) from paediatric patients diagnosed with T-cell ALL, we analysed DNA from 38 paediatric patients with T-ALL by nested polymerase chain reaction and electrophoresis. The STIL-TAL1 fusion gene was not detected in NBSs from any of the 38 patients with T-ALL, suggesting that STIL-TAL1 fusion genes are most probably postnatal events in paediatric T-ALL.

Hass HG, Vogel U, Scheurlen M, Jobst J
Use of Gene Expression Analysis for Discrimination of Primary and Secondary Adenocarcinoma of the Liver.
Oncology. 2018; 95(4):211-219 [PubMed] Related Publications
BACKGROUND: Due to late diagnosis and resistance to chemotherapy, most patients with cholangiocarcinoma have an unfavorable prognosis. Despite the use of immunohistochemistry (IHC) in clinical routine, differentiation between intrahepatic cholangiocarcinoma (ICC) and secondary adenocarcinomas of the liver is frequently not clear, leading to false diagnosis and treatment decisions.
METHODS: Oligonucleotide microarrays (Affymetrix Hu133A©) were used for gene expression analysis of ICC (n = 11) and secondary adenocarcinomas (colorectal metastases; n = 6). By two-dimensional cluster analysis a specific gene expression profile of these tumors was established and confirmed by real-time polymerase chain reaction and IHC.
RESULTS: A total of 338 genes were significantly dysregulated (gene expression/fc ≥2; dysregulation in ≥60%) in both tumor groups. Using two-dimensional cluster analysis a fast, clear, and reproducible differentiation between ICC and colorectal metastases was possible in all cases. As potential biomarkers for differentiation, twelve genes (ICC: KRT7, DBN1, LCTB, LIF, STK17A, PIGF; metastases: TDGF1, HOXA9, TFF3, MYB, ABP1, BCL11A) were detected and will be used for further investigations.
CONCLUSIONS: A specific gene expression profile for discrimination of primary and secondary adenocarcinoma of the liver could be established. In addition, marker genes for both cancers and their potential use as discrimination markers in clinical routine were also described partially for the first time.

Zhang L, Hu C, Zheng X, et al.
Oncocytic Schneiderian papilloma-associated adenocarcinoma and KRAS mutation: A case report.
Medicine (Baltimore). 2018; 97(23):e11025 [PubMed] Article available free on PMC after 02/10/2019 Related Publications
RATIONALE: Oncocytic Schneiderian papillomas (OSP) are an uncommon type of sinonasal papillomas that arise from the Schneiderian epithelium, accounting for only 6% of all sinonasal papillomas. Malignancies arising in OSP are rare and are almost always described as in situ or invasive squamous cell carcinoma, although mucoepidermoid, small cell carcinoma and sinonasal undifferentiated carcinoma have also been reported. To our knowledge, only 18 such instances have been reported in the medical literature.
PATIENT CONCERNS: Here, we report the case of an 81-year-old man presenting with a left sinonasal neoplasm, who had undergone 4 operations. The first postoperative pathology revealed a benign nasal polyp. The following several postoperative pathology revealed a novel, human papillomavirus-negative adenocarcinoma with increasing malignant features with each recurrence arising in an OSP. In addition, the most recent recurrences were associated with metastasis of cervical lymph nodes. And after the operation, the patient refused adjuvant radiotherapy. On 6-month follow-up after the last operation, the patient developed an in situ tumor recurrence 1 month after the fourth operation and refused to undergo surgery again.
DIAGNOSIS: Immunohistochemistry for Ki67, CK7, CK5/6, P53, and P63 showed a progression of malignancy. HPV assay presented the 21 most prevalent HPV types were negative. In addition, KRAS gene exon 2 G12C presented mutation in the OSP-associated adenocarcinoma.
INTERVENTIONS: During the whole course of the patient's disease, we performed four nasal endoscopic operations. And after the last operation, the patient refused adjuvant radiotherapy and KRAS-targeted therapy.
OUTCOMES: We are the first to describe adenocarcinoma arising in an OSP. To our surprise, from the first benign neoplasm to the second OSP-associated adenocarcinoma, it went through a long period of 10 years. However, after the adenocarcinogenesis, the differentiation of tumor became worse with the shorter interval of each recurrence.
LESSONS: Therefore, for elderly patients with unilateral nasal polyps, long-term follow-up is necessary. Once OSP turns into malignant, radical resection should be performed as much as possible to reduce the irritability of tumors.

Sato K, Mori R, Hiroshima Y, et al.
RT-PCR of peritoneal washings predicts peritoneal pancreatic cancer recurrence.
J Surg Res. 2018; 226:122-130 [PubMed] Related Publications
BACKGROUND: Peritoneal recurrence of pancreatic cancer is a frequent and lethal outcome after R0 resection. A method to predict peritoneal recurrence could be helpful in its prevention.
MATERIALS AND METHODS: Peritoneal washings were prospectively obtained from 29 patients in whom R0 resection was performed. Cytological examination (CY) and real-time reverse transcription polymerase chain reaction (RT-PCR) of the peritoneal washing for the detection of cancer-related genes, CEACAM5, KRT7, KRAS, and MUC1, were performed. Clinicopathological characteristics and real-time RT-PCR results of the peritoneal washing were compared between patients whose pancreatic cancer recurred peritoneally (n = 7) and those patients who it did not recur (n = 22).
RESULTS: Only one CY-positive (CY
CONCLUSIONS: High expression of MUC1 mRNA in peritoneal washings is a significant risk factor for peritoneal recurrence of pancreatic cancer after R0 resection along with poor disease-specific survival. RT-PCR of MUC1 mRNA in peritoneal washing may be useful for individualization of adjuvant chemotherapy.

Ngoc PCT, Tan SH, Tan TK, et al.
Identification of novel lncRNAs regulated by the TAL1 complex in T-cell acute lymphoblastic leukemia.
Leukemia. 2018; 32(10):2138-2151 [PubMed] Related Publications
TAL1/SCL is one of the most prevalent oncogenes in T-cell acute lymphoblastic leukemia (T-ALL). TAL1 and its regulatory partners (GATA3, RUNX1, and MYB) positively regulate each other and coordinately regulate the expression of their downstream target genes in T-ALL cells. However, long non-coding RNAs (lncRNAs) regulated by these factors are largely unknown. Here we established a bioinformatics pipeline and analyzed RNA-seq datasets with deep coverage to identify lncRNAs regulated by TAL1 in T-ALL cells. Our analysis predicted 57 putative lncRNAs that are activated by TAL1. Many of these transcripts were regulated by GATA3, RUNX1, and MYB in a coordinated manner. We identified two novel transcripts that were activated in multiple T-ALL cell samples but were downregulated in normal thymocytes. One transcript near the ARID5B gene locus was specifically expressed in TAL1-positive T-ALL cases. The other transcript located between the FAM49A and MYCN gene locus was also expressed in normal hematopoietic stem cells and T-cell progenitor cells. In addition, we identified a subset of lncRNAs that were negatively regulated by TAL1 and positively regulated by E-proteins in T-ALL cells. This included a known lncRNA (lnc-OAZ3-2:7) located near the RORC gene, which was expressed in normal thymocytes but repressed in TAL1-positive T-ALL cells.

Al-Maghrabi J, Emam E, Gomaa W
Immunohistochemical staining of cytokeratin 20 and cytokeratin 7 in colorectal carcinomas: Four different immunostaining profiles.
Saudi J Gastroenterol. 2018 Mar-Apr; 24(2):129-134 [PubMed] Article available free on PMC after 02/10/2019 Related Publications
Background/Aim: Aberrant expression of CK20/CK7 is reported in a percentage of colorectal carcinomas (CRC); however, its relation to clinicopathological variables and survival data is still unclear. The objective of this study is to explore patterns of CK20/CK7 immunostaining in CRC and to analyse the diagnostic, prognostic, and predictive role of patterns of CK20/CK7 immunostaining.
Materials and Methods: A total of 144 CRC cases were retrieved from the archives at the Department of Pathology, King Abdulaziz University, Jeddah, Saudi Arabia. Immunohistochemistry was performed using antibody to CK7 and CK20. Immunostaining was defined as low and high by using the extent of staining. The association of CK7 and CK20 with clinicopathological characteristics and survival.
Results: CK20 was expressed in a higher percentage of CRC and nodal metastasis than CK7. No difference in CK7 and CK20 immunostaining in primary and metastasis carcinomas was found. Four patterns of CK20/CK7 were identified; CK20+/CK7- (60.4%), CK20+/CK7+ (2.1%), CK20-/CK7- (35.4%), and CK20-/CK7+ (2.1%). There was no statistically significant correlation between CK20/CK7 immunohistochemical profile and clinicopathological characteristics, prognosis, and survival was determined.
Conclusions: Our results may support the heterogeneity of CRC. CRC showed four different subclasses following patterns of relative CK20/CK7 immunostaining. A considerable number of CRC expressed aberrant immune profile of CK20/CK7, which should be considered during diagnosing CRC in metastatic regions. Further studies on larger cohorts correlating different immunohistochemical cytokeratin profiles to molecular subtypes of CRC are recommended for better understanding of pathogenesis and behaviour of CRC.

Chen M, Liu P, Yan F, et al.
Distinctive features of immunostaining and mutational load in primary pulmonary enteric adenocarcinoma: implications for differential diagnosis and immunotherapy.
J Transl Med. 2018; 16(1):81 [PubMed] Article available free on PMC after 02/10/2019 Related Publications
BACKGROUND: Primary pulmonary enteric adenocarcinoma (PEAC) is an extremely rare variant of invasive lung cancer. It is highly heterogeneous while shares some common morphologic and immunohistochemical features with usual pulmonary adenocarcinoma (PAC) and colorectal adenocarcinoma (CRAC), making the differential diagnosis difficult. At present there are only limited studies about distinctive features of primary PEAC and the results are often inconsistent.
METHODS: We retrospectively analyzed total 129 primary PEACs and 50 CRACs that were published since 1991 or diagnosed in our centre. Among them eight typical samples of primary PEACs and usual PACs were detected by targeted exome sequencing.
RESULTS: The combination of CK7
CONCLUSIONS: The combination of CK7

Huang C, Zhang Z, Chen L, et al.
Acetylation within the N- and C-Terminal Domains of Src Regulates Distinct Roles of STAT3-Mediated Tumorigenesis.
Cancer Res. 2018; 78(11):2825-2838 [PubMed] Related Publications
Posttranslational modifications of mammalian c-Src N-terminal and C-terminal domains regulate distinct functions. Myristoylation of G

Panda PK, Naik PP, Praharaj PP, et al.
Abrus agglutinin stimulates BMP-2-dependent differentiation through autophagic degradation of β-catenin in colon cancer stem cells.
Mol Carcinog. 2018; 57(5):664-677 [PubMed] Related Publications
Eradicating cancer stem cells (CSCs) in colorectal cancer (CRC) through differentiation therapy is a promising approach for cancer treatment. Our retrospective tumor-specimen analysis elucidated alteration in the expression of bone morphogenetic protein 2 (BMP-2) and β-catenin during the colon cancer progression, indicating that their possible intervention through "forced differentiation" in colon cancer remission. We reveal that Abrus agglutinin (AGG) induces the colon CSCs differentiation, and enhances sensitivity to the anticancer therapeutics. The low dose AGG (max. dose = 100 ng/mL) decreased the expression of stemness-associated molecules such as CD44 and β-catenin in the HT-29 cell derived colonospheres. Further, AGG augmented colonosphere differentiation, as demonstrated by the enhanced CK20/CK7 expression ratio and induced alkaline phosphatase activity. Interestingly, the AGG-induced expression of BMP-2 and the AGG-induced differentiation were demonstrated to be critically dependent on BMP-2 in the colonospheres. Similarly, autophagy-induction by AGG was associated with colonosphere differentiation and the gene silencing of BMP-2 led to the reduced accumulation of LC3-II, suggesting that AGG-induced autophagy is dependent on BMP-2. Furthermore, hVps34 binds strongly to BMP-2, indicating a possible association of BMP-2 with the process of autophagy. Moreover, the reduction in the self-renewal capacity of the colonospheres was associated with AGG-augmented autophagic degradation of β-catenin through an interaction with the autophagy adaptor protein p62. In the subcutaneous HT-29 xenograft model, AGG profoundly inhibited the growth of tumors through an increase in BMP-2 expression and LC3-II puncta, and a decrease in β-catenin expression, confirming the antitumor potential of AGG through induction of differentiation in colorectal cancer.

Takamatsu M, Sato Y, Muto M, et al.
Hyalinizing clear cell carcinoma of the bronchial glands: presentation of three cases and pathological comparisons with salivary gland counterparts and bronchial mucoepidermoid carcinomas.
Mod Pathol. 2018; 31(6):923-933 [PubMed] Related Publications
Hyalinizing clear cell carcinoma of the bronchial glands is a very rare tumor. Since only five reports describing six tumors have been published to date, only a little is known about specific histologic findings and clinical features. Because of its rarity, hyalinizing clear cell carcinoma has not been described in the latest WHO classification of pulmonary tumors yet. Here we present three cases of bronchial hyalinizing clear cell carcinomas, confirmed by both fluorescence in situ hybridization (FISH) and RT-PCR, focusing on histologic and immunohistochemical characteristics in a comparison with three cases of salivary gland origin. In addition, we compared immunohistochemical features with bronchial mucoepidermoid carcinoma, a lesion that needs to be taken into account in differential diagnosis of hyalinizing clear cell carcinoma. All our bronchial hyalinizing clear cell carcinoma cases were surgically resected. Histologically, tumor cells showed clear to eosinophilic cytoplasm with hyalinizing stroma in various proportions, resembling those of salivary gland origin. Immunohistochemically, tumor cells were positive for CK7, CK5/6, p40, p63, and ATF1, while they were negative for TTF1, Napsin A, HMB45, and SOX10. The CK5/6 staining pattern varied in mucoepidermoid carcinomas, while that of hyalinizing clear cell carcinoma was uniformly positive. FISH revealed EWSR1-ATF1 fusion, and RT-PCR with sequencing confirmed specificity of the chimeric gene for hyalinizing clear cell carcinoma. Clinically, bronchial hyalinizing clear cell carcinoma was characterized by occurrence in the fourth to sixth decades, no link with smoking history, and a predilection for the right lung, in line with previous reports. In summary, our study confirmed that the bronchial hyalinizing clear cell carcinoma is a histologically and genetically identical tumor to that of salivary gland origin, and that gene rearrangement analysis can play a critical role in distinction from mucoepidermoid carcinoma.

Leong WZ, Tan SH, Ngoc PCT, et al.
ARID5B as a critical downstream target of the TAL1 complex that activates the oncogenic transcriptional program and promotes T-cell leukemogenesis.
Genes Dev. 2017; 31(23-24):2343-2360 [PubMed] Article available free on PMC after 02/10/2019 Related Publications
The oncogenic transcription factor

Laco J, Kovarikova H, Chmelarova M, et al.
Analysis of DNA methylation and microRNA expression in NUT (nuclear protein in testis) midline carcinoma of the sinonasal tract: a clinicopathological, immunohistochemical and molecular genetic study.
Neoplasma. 2018; 65(1):113-123 [PubMed] Related Publications
The aim of this study was a detailed clinicopathological investigation of sinonasal NUT midline carcinoma (NMC), including analysis of DNA methylation and microRNA (miRNA) expression. Three (5%) cases of NMC were detected among 56 sinonasal carcinomas using immunohistochemical screening and confirmed by fluorescence in situ hybridization. The series comprised 2 males and 1 female, aged 46, 60, and 65 years. Two tumors arose in the nasal cavity and one in the maxillary sinus. The neoplasms were staged pT1, pT3, and pT4a (all cN0M0). All patients were treated by radical resection with adjuvant radiotherapy. Two patients died 3 and 8 months after operation, but one patient (pT1 stage; R0 resection) experienced no evidence of disease at 108 months. Microscopically, all tumors consisted of infiltrating nests of polygonal cells with vesicular nuclei, prominent nucleoli and basophilic cytoplasm. Abrupt keratinization was present in only one case. Immunohistochemically, there was a diffuse expression of cytokeratin (CK) cocktail, CK7, p40, p63, and SMARCB1/INI1. All NMCs tested negative for EBV and HPV infection. Two NMCs showed methylation of RASSF1 gene. All other genes (APC, ATM, BRCA1, BRCA2, CADM1, CASP8, CD44, CDH13, CDKN1B, CDKN2A, CDKN2B, CHFR, DAPK1, ESR1, FHIT, GSTP1, HIC1, KLLN, MLH1a, MLH1b, RARB, TIMP3, and VHL) were unmethylated. All NMCs showed upregulation of miR-9 and downregulation of miR-99a and miR-145 and two cases featured also upregulation of miR-21, miR-143, and miR-484. In summary, we described three cases of sinonasal NMCs with novel findings on DNA methylation and miRNA expression, which might be important for new therapeutic strategies in the future.

Cai X, Xiong J, Hu QG, et al.
Look into hepatic progenitor cell associated trait: Histological heterogeneity of hepatitis B-related combined hepatocellular-cholangiocarcinoma.
J Huazhong Univ Sci Technolog Med Sci. 2017; 37(6):873-879 [PubMed] Related Publications
Combined hepatocellular-cholangiocarcinoma (CHC) is a mixed tumor containing elements of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). Its remarkable histological heterogeneity has been linked to putative hepatic progenitor cell (HPC) origin. However, detailed histological or phenotypic description is rarely documented. In the present study, we reassessed 68 cases previously diagnosed as hepatitis B-related CHCs by immunohistochemistry and double-fluorescence immunostaining, focusing on HPC associated phenotypic observation of intermediate area of the tumor. It was found that tumor cells showed remarkable heterogeneity in intermediate area. Tumor cells with intermediate morphology between hepatocytes and cholangiocytes were oval-shaped and small with scant cytoplasm and hyperchromatic nuclei, arranging in solid nests mostly. By Keratin 7 (K7) staining, it appeared that the nests of tumor cells represented a maturation process from the undifferentiated small cells to mature hepatocytes through the "transitional" cells. Then, these small cells were further confirmed with intermediate phenotype as HPC by exploring immature hepatocellular marker and HPC/biliary markers co-localization. In conclusion, the HPC associated trait in CHC can be interpreted by HPC origin or gain of "stemness" by dedifferentiation. It is still too soon to give a final word that it is innate or acquired signature of HPC associated trait in CHC.

Bao Y, Li J, Zhu Y
Mammary Analog Secretory Carcinoma With ETV6 Rearrangement Arising in the Conjunctiva and Eyelid.
Am J Dermatopathol. 2018; 40(7):531-535 [PubMed] Related Publications
Mammary analog secretory carcinoma (MASC) of salivary gland is a recently described neoplasm that morphologically and immunohistochemically resembles secretory carcinoma of the breast. Genetically, both of them harbor ETV-6-NTRK-3 fusion rearrangement. One case of primary MASCs arising from the eyelid is reported. The patient was a 52-year-old man. Microscopically, the tumor exhibited nodular aggregation of solid, tubular, and microcystic/macrocystic structures. Characteristic "colloid-like" eosinophilic secretory material was present within intraluminal spaces. Immunohistochemically, the tumor cells were positive for mammaglobin, S-100, STAT5a, vimentin, GCDFP-15, AE1/AE3, EMA, and CK7 and were negative for DOG-1, CK5/6, and SMA. A dual color break-apart fluorescence in situ hybridization probe identified rearrangement of the ETV6 gene locus on chromosome 12. The patient had no history of breast or salivary gland tumor. The tumor was completely excised, and the patient has no evidence of recurrent disease or metastasis after 1-year follow-up. A diagnosis of primary MASC was rendered. MASC has never been reported occurring in ocular region. This type of secretory carcinoma probably originates from sweat glands or accessory lacrimal glands, Wolfring and Krause. This unique case expands the clinicopathologic landscape of MASCs for better characterization of this rare entity.

Dulskas A, Al Bandar M, Choi YY, et al.
A case of gastric cancer metastasis to the breast in a female with BRCA2 germline mutation and literature review.
Acta Chir Belg. 2019; 119(1):59-63 [PubMed] Related Publications
INTRODUCTION: Gastric cancer is a deadly disease. Common sites of distant metastasis of gastric cancer are the peritoneum, liver, lymph nodes, and lung. The breast is a rare site of metastasis in gastric cancer which occurs in males dominantly.
PATIENTS AND METHODS: Here, we report the first case of metastatic gastric cancer to the breast in a patient with the breast cancer 2 (BRCA2) germline mutation. A 34-year-old female was admitted to the hospital with dyspepsia and a palpable mass in the left breast. Gastric cancer was confirmed to be signet ring cell adenocarcinoma. The breast mass exhibited histological properties consistent with gastric cancer. Immunohistochemistry results showed the breast tumor was CDX-2 and CK20-positive, but ER-, CK7-, and GATA3-negative. The BRCA1 gene had a wild-type sequence, but a heterozygous variant was discovered in BRCA2 in exon 10 (c.1744A > C, p.T582P); the significance of this variant is unknown.
RESULTS: The patient received palliative XELOX (capecitabine + oxaliplatin) with radiation therapy to the stomach. The breast tumor resolved completely, but the overall response was partial.
CONCLUSION: Gastric cancer metastasis to the breast is rare, but should be considered in young female patients with signet ring cell type gastric cancer.

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