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S100A1; S100 calcium binding protein A1 (1q21)

Gene Summary

Gene:S100A1; S100 calcium binding protein A1
Aliases: S100, S100A, S100-alpha
Location:1q21
Summary:The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100 genes include at least 13 members which are located as a cluster on chromosome 1q21. This protein may function in stimulation of Ca2+-induced Ca2+ release, inhibition of microtubule assembly, and inhibition of protein kinase C-mediated phosphorylation. Reduced expression of this protein has been implicated in cardiomyopathies. [provided by RefSeq, Jul 2008]
Databases:OMIM, VEGA, HGNC, Ensembl, GeneCard, Gene
Protein:protein S100-A1
HPRD
Source:NCBI
Updated:14 December, 2014

Gene
Ontology:

What does this gene/protein do?
Show (12)

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.

  • Cell Differentiation
  • Sensitivity and Specificity
  • Leiomyosarcoma
  • S100 Proteins
  • Transcription
  • Gene Expression
  • Neoplasm Proteins
  • Polymerase Chain Reaction
  • Melanoma-Specific Antigens
  • S100A1
  • Early Diagnosis
  • RTPCR
  • Kidney
  • Calcium-Binding Proteins
  • Translocation
  • Base Sequence
  • Uterus
  • Chromosome 1
  • Lung Cancer
  • Staging
  • Differential Diagnosis
  • Gene Expression Profiling
  • Adenoma, Oxyphilic
  • Messenger RNA
  • Tumor Markers
  • Kidney Cancer
  • Renal Cell Carcinoma
  • Cancer Gene Expression Regulation
  • X Chromosome Inactivation
  • Transfection
  • Bladder Cancer
  • Immunohistochemistry
  • Cancer RNA
  • DNA Primers
  • Proto-Oncogene Proteins c-kit
  • Ovarian Cancer
  • Squamous Cell Carcinoma
  • Microphthalmia-Associated Transcription Factor
  • Up-Regulation
  • Leiomyoma
  • Oligonucleotide Array Sequence Analysis
Tag cloud generated 14 December, 2014 using data from PubMed, MeSH and CancerIndex

Notable (1)

Scope includes mutations and abnormal protein expression.

Entity Topic PubMed Papers
Bladder CancerS100A1 and Bladder Cancer View Publications1

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: S100A1 (cancer-related)

Yordanov A, Ivanov I, Popovska S, et al.
[Evaluation of the expression of S100A1 protein in serous, mucinous and endometroid ovarian carcinoma].
Akush Ginekol (Sofiia). 2013; 52(5):22-6 [PubMed] Related Publications
According to literature approximately 60% from all ovarian malignances express epithelial phenotype. According to their histomorphological characteristics, epithelial ovarian tumors are divided into eight groups. In some particular cases, separate histological types are hard to distinguish one from another. Recent studies show the presence of beneficial effect of adjuvant radiotherapy on most of the early ovarian carcinomas (all, except serous carcinomas). In renal cell carcinomas SI00A 1 is used to distinguish between different subtypes of the malignancy. Forty cases of ovarian carcinomas were analyzed in a retrospective study. Immunohistochemical evaluation of the S100A1 protein expression was carried out on representative archival formalin -fixed -paraffin-embedded tissue materials. Positivity for S100A1 was observed in 31 (77.50%) of the studied cases. Twenty-seven out of thirty-two (84.38%) cases of serous ovarian carcinoma were found to express S100A1. S100A1 expression was observed in one out of the two mucinous and three out of the six endometroid ovarian carcinomas. Immunopositivity was nuclear, cytoplasmic or nuclear and cytoplasmic in serous carcinomas, nuclear in the one positive mucinous carcinoma and sytoplasmic in the three imunopositive endometroid ovarian carcinomas. The S100A1 immunohistochemical marker is not likely to be useful in clinical practice to distinguish between different histological subtypes of ovarian cancer. The large percentage of S100A1 positivity in serous ovarian carcinomas needs a better understanding.

Related: Ovarian Cancer


López JI, Schiavo-Lena M, Corominas-Cishek A, et al.
Nephrogenic adenoma of the urinary tract: clinical, histological, and immunohistochemical characteristics.
Virchows Arch. 2013; 463(6):819-25 [PubMed] Related Publications
Nephrogenic adenoma is a benign condition of the urinary tract resulting from the displacement and seeding of renal tubular cells from the renal pelvis to the urethra. A retrospective series of 134 cases collected from four hospitals in three different countries was analyzed in this study. Recorded clinical data included age and sex, topography, urological antecedents, coexistent lesions, and follow-up. Cytonuclear and architectural features were reviewed, and PAX-8, p63, PSMA, S100A1, CEA, EMA, CD117, cannabinoid receptor CB1, AMACR, E-cadherin, and CD10 antibodies were included in an immunohistochemical panel. Males predominated (105 M/29 F) with an average age of 66 years (range, 14-96). Urothelial carcinoma was the most frequent clinical antecedent (43.2 %) and also the most common coexisting lesion (14 %). Tubular architecture was the most frequent pattern detected (40 %) although most cases showed a mixed pattern (45.5 %). Deep infiltrative growth into the muscularis propria occurred in two cases. EMA and PAX-8 were expressed in 100 % of nephrogenic adenomas, while E-cadherin reactivity was observed in 66.6 % of cases, cannabinoid receptor CB1 in 25 %, CD10 in 13.6 %, CD117 in 4.1 %, and AMACR in 2.7 %. For the rest of the antigens, no reactivity was found. The average time lapse between the pathological antecedent and the discovery of a nephrogenic adenoma was 32 months. We conclude that nephrogenic adenoma displays a broad spectrum of histological features that may mimic malignancy. In our experience, CB1 immunostaining adds a further argument in favor of a renal origin of this lesion. The combination of PAX-8+, p63-, and EMA + distinguishes nephrogenic adenoma from urothelial and prostate carcinoma, its most frequent malignant look-alikes.

Related: Urinary System Cancers


Lyle M, Long GV
Diagnosis and treatment of KIT-mutant metastatic melanoma.
J Clin Oncol. 2013; 31(26):3176-81 [PubMed] Related Publications
A 52-year-old man has unresectable locally recurrent melanoma of the left foot (Fig 1) and pulmonary metastases. Nine months before this presentation, he underwent a wide local excision and sentinel node biopsy for an acral melanoma on his left heel. Pathology disclosed Breslow thickness of 4.8 mm, Clark level IV, and tumor ulceration with a mitotic rate of 37 mitoses/mm(2). Both sentinel nodes in the left groin were positive for melanoma cells, which expressed S100, HMB45, and melan A. At subsequent left inguinal dissection, seven more nodes showed no additional nodal metastases. Within 3 months of his original surgery, the patient developed a local recurrence in the foot, and over the subsequent 6 months, he underwent serial local excisions and topical diphencyprone treatment. A recent staging scan showed at least 20 foci of in-transit disease in the left lower leg and foot, as well as a solitary lung metastasis (12 mm). His Eastern Cooperative Oncology Group performance status is 1, with no significant comorbidities. High-resolution melt followed by sequencing of an in-transit metastasis showed there is no BRAF exon 15 mutation. However, Sanger sequencing of KIT exons 9, 11, 13, and 17, performed as screening for a clinical trial enrolling patients with metastatic acral and mucosal melanomas, showed an exon 13 K642E mutation.

Related: Lung Cancer MLANA Melanoma Skin Cancer


Plantier F
[Granular cell tumour or Abrikissoff's tumour].
Ann Dermatol Venereol. 2013; 140(5):399-402 [PubMed] Related Publications


Quinones W, Ziober A, Yao Y, Bing Z
Immunohistochemical markers for the differential diagnosis of nephrogenic adenomas.
Ann Diagn Pathol. 2013; 17(1):41-4 [PubMed] Related Publications
Nephrogenic adenoma (NA) is a rare benign lesion commonly occurring in the urinary bladder that poses challenges to devising a diagnosis. In this study, 21 cases of NAs were studied by performing immunohistochemistry for PAX8, p63, CK903, PSA, S100A1, BerEP4, and CEA on routine tissue sections. PAX8 showed diffuse moderate to strong (2+ and 3+) nuclear staining in all of NAs (n = 6 and 15, respectively) and negative in the normal urothelium (n = 15). Nuclear staining for p63 was not seen in any case of NAs examined (n = 19) and was diffuse and strong (3+) in the normal urothelium (n = 14). High-molecular-weight keratin CK903 showed weak (1+) diffuse staining in all of the NAs examined (n = 19) and diffuse and moderate to strong positivity in the normal urothelium (n = 16). PSA staining was negative in both of the NAs (n = 21) and normal urothelium (n = 16). S100A1 showed strong (3+) diffuse staining in 19 of 20 of the NAs examined (n = 19) and diffuse weak (1+) (n = 14) to moderate (n = 3) staining in the normal urothelium. BerEP4 showed focal to diffuse, mild to moderate (1+ and 2+) cytoplasmic staining in all of NAs (n = 2 and 19) and negative in the normal urothelium (n = 19). CEA staining was negative in both of the NAs (n = 21) and normal urothelium (n = 17). A panel composed of PAX8, p63, PSA, S100A1, and CEA appears to be sensitive and specific in differentiating NA from its mimics of urothelial and prostatic origins.

Related: Bladder Cancer Bladder Cancer - Molecular Biology PAX8 gene


Rizzardi AE, Johnson AT, Vogel RI, et al.
Quantitative comparison of immunohistochemical staining measured by digital image analysis versus pathologist visual scoring.
Diagn Pathol. 2012; 7:42 [PubMed] Free Access to Full Article Related Publications
UNLABELLED: Immunohistochemical (IHC) assays performed on formalin-fixed paraffin-embedded (FFPE) tissue sections traditionally have been semi-quantified by pathologist visual scoring of staining. IHC is useful for validating biomarkers discovered through genomics methods as large clinical repositories of FFPE specimens support the construction of tissue microarrays (TMAs) for high throughput studies. Due to the ubiquitous availability of IHC techniques in clinical laboratories, validated IHC biomarkers may be translated readily into clinical use. However, the method of pathologist semi-quantification is costly, inherently subjective, and produces ordinal rather than continuous variable data. Computer-aided analysis of digitized whole slide images may overcome these limitations. Using TMAs representing 215 ovarian serous carcinoma specimens stained for S100A1, we assessed the degree to which data obtained using computer-aided methods correlated with data obtained by pathologist visual scoring. To evaluate computer-aided image classification, IHC staining within pathologist annotated and software-classified areas of carcinoma were compared for each case. Two metrics for IHC staining were used: the percentage of carcinoma with S100A1 staining (%Pos), and the product of the staining intensity (optical density [OD] of staining) multiplied by the percentage of carcinoma with S100A1 staining (OD*%Pos). A comparison of the IHC staining data obtained from manual annotations and software-derived annotations showed strong agreement, indicating that software efficiently classifies carcinomatous areas within IHC slide images. Comparisons of IHC intensity data derived using pixel analysis software versus pathologist visual scoring demonstrated high Spearman correlations of 0.88 for %Pos (p < 0.0001) and 0.90 for OD*%Pos (p < 0.0001). This study demonstrated that computer-aided methods to classify image areas of interest (e.g., carcinomatous areas of tissue specimens) and quantify IHC staining intensity within those areas can produce highly similar data to visual evaluation by a pathologist.
VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1649068103671302.

Related: Ovarian Cancer


Cmoch A, Groves P, Palczewska M, Pikuła S
S100A proteins in propagation of a calcium signal in norm and pathology.
Postepy Biochem. 2012; 58(4):429-36 [PubMed] Related Publications
Calcium ions are essential factors controlling the balance between cell survival, growth, differentiation and metabolism. Ca2+ acts as a global second messenger involved in the regulation of all aspects of cell function. Fluctuations in the intra- and extracellular Ca2+ concentration [Ca2+] in response to different environmental stimuli drive most cellular functions. Therefore, sustenance of calcium homeostasis requires perfect organization in time and space that is achieved by calcium binding proteins (CaBPs). These proteins are involved in sensing and transforming calcium signals to downstream cellular responses. Growing number of evidence suggests than many human disorders, including cancer progression, are related to deregulation of cellular calcium homeostasis and defects in CaBPs functions. In this review we will focus on the roles of S100A proteins in intracellular and extracellular calcium signalling and homeostasis. The S100A subfamily is among the most distinctive of EF-hand CaBPs and are found exclusively in vertebrates. They are believed to have evolved to enable activation of specific biochemical pathways in parallel to the activity of Ca2+ sensors such as calmodulin and/or annexins. The importance of S100 proteins is underscored by their deregulated expression in neurodegenerative and inflammatory disorders, myopathies and cancer. In addition, S100 proteins serve as diagnostic markers in the clinic and are under constant investigation. Their roles and the roles of the S100A protein partners in normal and pathology will be also discussed.

Related: Cancer Prevention and Risk Reduction


Balluff B, Rauser S, Meding S, et al.
MALDI imaging identifies prognostic seven-protein signature of novel tissue markers in intestinal-type gastric cancer.
Am J Pathol. 2011; 179(6):2720-9 [PubMed] Free Access to Full Article Related Publications
Proteomics-based approaches allow us to investigate the biology of cancer beyond genomic initiatives. We used histology-based matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry to identify proteins that predict disease outcome in gastric cancer after surgical resection. A total of 181 intestinal-type primary resected gastric cancer tissues from two independent patient cohorts were analyzed. Protein profiles of the discovery cohort (n = 63) were directly obtained from tumor tissue sections by MALDI imaging. A seven-protein signature was associated with an unfavorable overall survival independent of major clinical covariates. The prognostic significance of three individual proteins identified (CRIP1, HNP-1, and S100-A6) was validated immunohistochemically on tissue microarrays of an independent validation cohort (n = 118). Whereas HNP-1 and S100-A6 were found to further subdivide early-stage (Union Internationale Contre le Cancer [UICC]-I) and late-stage (UICC II and III) cancer patients into different prognostic groups, CRIP1, a protein previously unknown in gastric cancer, was confirmed as a novel and independent prognostic factor for all patients in the validation cohort. The protein pattern described here serves as a new independent indicator of patient survival complementing the previously known clinical parameters in terms of prognostic relevance. These results show that this tissue-based proteomic approach may provide clinically relevant information that might be beneficial in improving risk stratification for gastric cancer patients.

Related: Stomach Cancer Gastric Cancer


Li J, Riau AK, Setiawan M, et al.
S100A expression in normal corneal-limbal epithelial cells and ocular surface squamous cell carcinoma tissue.
Mol Vis. 2011; 17:2263-71 [PubMed] Free Access to Full Article Related Publications
PURPOSE: To study the expression and cellular distribution of multiple S100A genes and proteins in normal corneal-limbal epithelium and ocular surface squamous cell carcinoma (SCC) tissue.
METHODS: Normal corneal-limbal tissue was obtained from the Lions Eye Bank, Tampa, FL. Ocular surface SCC tissues were excised from patients undergoing surgery at Singapore National Eye Centre. S100A mRNA expression was measured by quantitative PCR. S100 protein distribution was determined by immunofluorescent staining analysis.
RESULTS: Twelve S100 mRNAs were identified in human corneal and limbal epithelial cells. S100A2, A6, A8, A9, A10, and A11 mRNA was expressed at high level, while S100A1, A3, A4, A5, A6, A7, and A12 mRNA expression was low. The intracellular localization of S100A2, A6, A8, A9, A10 and A11 protein was determined in normal corneal-limbal and SCC tissues. S100A2 and S100A10 proteins were enriched in basal limbal epithelial cells of the normal tissue. S100A8 and S100A9 were found only at the surface of peripheral corneal and limbal epithelium. S100A6 was uniformly found at the plasma membrane of corneal and limbal epithelial cells. S100A11 was found at the supralayer limbal epithelial cells adjacent to the conjunctiva. SCC tissue showed typical pathological changes with expression of cytokeartin (CK) 14 and CK4 in the epithelial cells. All SCC epithelial cells were positive of S100A2, S100A10, S100A6 and S100A11 staining. Intracellular staining of S100A8 and S100A9 was found in several layers of SCC epithelium. Expression of S100A2 and S100A10 decreased dramatically in cultured limbal epithelial cells with increased passaging, which was accompanied by a small increase of S100A9 mRNA, with no changes of S100A8 gene expression. Serum and growth hormone depletion of the culture serum caused a small reduction of S100A2 and S100A10 gene expression, which was accompanied by a small increase of S100A9 mRNA while no changes of S100A8 expression was measured.
CONCLUSIONS: Normal corneal and limbal epithelial cells express a broad spectrum of S100 genes and proteins. Ocular surface SCC express high levels of S100A2, S100A10, S100A8 and S100A9 proteins. The expression of S100A2 and S100A10 is associated with limbal epithelial cell proliferation and differentiation.


Kuroda N, Kanomata N, Yamaguchi T, et al.
Immunohistochemical application of S100A1 in renal oncocytoma, oncocytic papillary renal cell carcinoma, and two variants of chromophobe renal cell carcinoma.
Med Mol Morphol. 2011; 44(2):111-5 [PubMed] Related Publications
S100A1 is a calcium-binding protein and a member of the S100 family. Recently, S100A1 immunohistochemistry may be an available marker in the differential diagnosis between renal oncocytoma and chromophobe renal cell carcinoma (RCC). However, there are no reports on S100A1 expression in oncocytic papillary RCC that has been recently identified. In this article, we immunohistochemically examined the expression of S100A1 protein in 18 renal tumors including 4 renal oncocytoma, 10 chromophobe RCCs, and 4 oncocytic papillary RCCs. All the cases of renal oncocytoma and oncocytic papillary RCC showed a positive reaction for S100A1 with cytoplasmic pattern. In chromophobe RCC, 3 of 4 tumors with typical variant and 4 of 6 tumors in eosinophilic variant were completely negative for S100A1. Finally, S100A1 immunohistochemistry may be useful in distinguishing renal oncocytoma from chromophobe RCC, but it may be of no use in the differential diagnosis between renal oncocytoma and oncocytic papillary RCC.

Related: Kidney Cancer


Wang JM, Zhang YF, Yang R, Wang YP
[Bilateral multifocal hybrid oncocytic romophobe tumor of the kidney: report of a case].
Zhonghua Bing Li Xue Za Zhi. 2011; 40(2):123-4 [PubMed] Related Publications


Related: Kidney Cancer


Kuroda N, Kawada C, Tamura K, et al.
Re-evaluation of histological type by immunohistochemical and genetic study of transcription factors (TFE3 and TFEB) of VHL gene mutation-negative clear cell renal cell carcinoma and other special types of renal tumor.
Med Mol Morphol. 2011; 44(1):46-51 [PubMed] Related Publications
Translocation-type renal carcinoma has been recently discovered, and it is possible that this tumor may have been previously diagnosed as other types of renal tumor. We have subjected 41 renal tumors, including VHL gene mutation-negative clear cell renal cell carcinoma (RCC), papillary RCC, and chromophobe RCC, to immunohistochemistry of transcription factor E3 (TFE3) and TFEB. All tumors were histologically evaluated by additional immunohistochemical study. As a result, 5 tumors showed a positive reaction for TFE3 with a range from 1+ to 2+ in intensity. No tumors were positive for TFEB. In 5 tumors immunohistochemically positive for TFE3, chimeric transcripts including ASPL-TFE3, PRCC-TFE3, CLTCTFE3, PSF-TFE3, or Nono-TFE3 were not detected. The diagnosis of 6 tumors was changed by reevaluation through retrospective histological and immunohistochemical study. In 4 of 6 tumors, the diagnosis of clear cell RCC was changed to chromophobe RCC. In 1 tumor, oncocytoma was detectable, and RCC with rhabdoid features and sarcomatoid changes was detected in 1 tumor. Finally, the cutoff value of TFE3 immunohistochemistry should be more than 2+ with a wide range. The translocation-type renal carcinoma seems to be quite rare.

Related: Kidney Cancer MLANA VHL


Carvalho JC, Wasco MJ, Kunju LP, et al.
Cluster analysis of immunohistochemical profiles delineates CK7, vimentin, S100A1 and C-kit (CD117) as an optimal panel in the differential diagnosis of renal oncocytoma from its mimics.
Histopathology. 2011; 58(2):169-79 [PubMed] Related Publications
AIMS: To develop an immunohistochemical strategy for distinguishing renal oncocytoma (RO) from the eosinophilic variant of chromophobe (ChRCC), and papillary (PRCC) and clear cell (CRCC) renal cell carcinoma containing eosinophilic cytoplasm in core biopsy specimens.
METHODS AND RESULTS: Cluster analysis was performed on immunohistochemical data from 21 RO, 16 ChRCC, 16 CRCC and 20 PRCC patients. A panel of CK7, C-kit, S100A1 and vimentin clustered into four groups. Cluster A (94% ChRCC) expressed C-kit and CK7 and lacked S100A1 and vimentin. Cluster B (95% RO) expressed C-kit, S100A1, focal CK7 (single or small clusters of cells) and lacked vimentin. Cluster C comprised a mixture of PRCC and CRCC with no expression of C-kit or CK7 and variable S100A1 and vimentin. PRCC with strong expression of CK7 clustered into group D. A panel of S100A1 (positive) and focal CK7 expression distinguished RO from ChRCC with 91% sensitivity and 93% specificity. A panel of vimentin (negative) and C-kit (positive) distinguished RO from CRCC with 83% sensitivity and 86% specificity and RO from PRCC with 79% sensitivity and 88% specificity.
CONCLUSIONS: Hierarchical cluster analysis is an effective approach to analyse high-volume immunohistochemical data to generate an optimal panel in the differential diagnosis of oncocytoma from its mimics.

Related: Kidney Cancer


Truong LD, Shen SS
Immunohistochemical diagnosis of renal neoplasms.
Arch Pathol Lab Med. 2011; 135(1):92-109 [PubMed] Related Publications
CONTEXT: Histologic diagnosis of renal neoplasm is usually straightforward by routine light microscopy. However, immunomarkers may be essential in several contexts, including differentiating renal from nonrenal neoplasms, subtyping of renal cell carcinoma (RCC), and diagnosing rare types of renal neoplasms or metastatic RCC in small biopsy specimens.
OBJECTIVE: To provide a comprehensive review of the diagnostic utility of immunomarkers for renal neoplasms.
DESIGN: This review is based on published literature and personal experience.
CONCLUSIONS: The following markers may have diagnostic utility in various diagnostic contexts: cytokeratins, vimentin, α-methylacyl coenzyme A racemase, carbonic anhydrase IX, PAX2, PAX8, RCC marker, CD10, E-cadherin, kidney-specific cadherin, parvalbumin, claudin-7, claudin-8, S100A1, CD82, CD117, TFE3, thrombomodulin, uroplakin III, p63, and S100P. Cytokeratins are uniformly expressed by RCC, albeit in a somewhat limited amount in some subtypes, requiring broad-spectrum anti-CK antibodies, including both low- and high-molecular-weight cytokeratins. PAX2 and PAX8 are sensitive and relatively specific markers for renal neoplasm, regardless of subtype. CD10 and RCC marker are sensitive to renal cell neoplasms derived from proximal tubules, including clear cell and papillary RCCs. Kidney-specific cadherin, parvalbumin, claudin-7, and claudin-8 are sensitive markers for renal neoplasms from distal portions of the nephron, including chromophobe RCC and oncocytoma. CK7 and α-methylacyl coenzyme A racemase are sensitive markers for papillary RCC; TFE3 expression is essential in confirming the diagnosis of Xp11 translocation RCC. The potentially difficult differential diagnosis between chromophobe RCC and oncocytoma may be facilitated by S100A1 and CD82. Thrombomodulin, uroplakin III, p63, and S100P are useful markers for urothelial carcinoma. Together with high-molecular-weight cytokeratins, PAX2, and PAX8, they can help differentiate renal pelvic urothelial carcinoma from collecting duct RCC. A sensitive marker for sarcomatoid RCC is still not available. Immunomarkers are most often used for diagnosing metastatic RCC. Compared with primary RCC, expression of the above-mentioned markers is often less frequent and less diffuse in the metastatic setting. Recognizing the variable sensitivity and specificity of these markers, it is important to include at least CD10, RCC marker, PAX2, and PAX8 in the diagnostic panel.

Related: Kidney Cancer


McKiernan E, McDermott EW, Evoy D, et al.
The role of S100 genes in breast cancer progression.
Tumour Biol. 2011; 32(3):441-50 [PubMed] Related Publications
The S100 gene family encode low molecular weight proteins implicated in cancer progression. In this study, we analyzed the expression of four S100 genes in one cohort of patients with breast cancer and 16 S100 genes in a second cohort. In both cohorts, the expression of S100A8 and S1009 mRNA level was elevated in high-grade compared to low-grade tumors and in estrogen receptor-negative compared to estrogen receptor-positive tumors. None of the S100 transcripts investigated were significantly associated with the presence of lymph node metastasis. Notably, multiple S100 genes, including S100A1, S100A2, S100A4, S100A6, S100A8, S100A9, S100A10, S100A11, and S100A14 were upregulated in basal-type breast cancers compared to non-basal types. Using Spearman's correlation analysis, several S100 transcripts correlated significantly with each other, the strongest correlation has been found between S100A8 and S100A9 (r = 0.889, P < 0.001, n = 295). Of the 16 S100 transcripts investigated, only S100A11 and S100A14 were significantly associated with patient outcome. Indeed, these two transcripts predicted outcome in the cohort of patients that did not receive systemic adjuvant therapy. Based on our findings, we conclude that the different S100 genes play varying roles in breast cancer progression. Specific S100 genes are potential targets for the treatment of basal-type breast cancers.

Related: Breast Cancer


Ivan D, Prieto VG
Use of immunohistochemistry in the diagnosis of melanocytic lesions: applications and pitfalls.
Future Oncol. 2010; 6(7):1163-75 [PubMed] Related Publications
The accurate diagnosis of melanocytic lesions is essential for the adequate clinical management of the patients. Besides the histopathologic examination, immunohistochemical studies are often used as an adjunct in distinguishing melanocytic lesions from tumors with different origin or between benign and malignant melanocytic lesions. In the first part of this article, we analyze data on currently used immunohistochemical markers, with special emphasis on their applicability to clinical practice, and underline their potential pitfalls. The pathogenesis of malignant transformation of melanocytes is not completely understood. Recent studies report that various melanoma progression markers are preferentially expressed in benign or malignant melanocytic lesions or show different expression in subsequent stages of tumor development. Furthermore, in recent years, emerging genetic studies suggest that there are distinctive patterns of chromosomal aberrations in different subtypes of melanoma that can be altered by newly developed targeted therapies. In the second part of our article, we will discuss the most significant progression markers in melanoma that can be detected by immunohistochemistry and their potential usefulness for diagnosis, prognosis, staging or as therapeutic targets.

Related: Melanoma


Gobbo S, Eble JN, Delahunt B, et al.
Renal cell neoplasms of oncocytosis have distinct morphologic, immunohistochemical, and cytogenetic profiles.
Am J Surg Pathol. 2010; 34(5):620-6 [PubMed] Related Publications
This study was undertaken to elucidate the genetic patterns of the renal cell neoplasms of oncocytosis and to compare them with those found in cases with multiple oncocytomas. Three cases of renal oncocytosis and 6 cases of multiple oncocytomas were analyzed. Fluorescence in situ hybridization analysis was performed with centromeric probes for chromosomes 1, 2, 6, 10, and 17 that are typically lost in chromophobe renal cell carcinoma but not in oncocytoma. Immunohistochemistry for cytokeratin 7, parvalbumin, and S100A1 was performed in all cases. Eleven tumors were present in the 3 kidneys with oncocytosis. One of these was a classic chromophobe renal cell carcinoma. In the other 10, none showed any chromosomal losses, whereas 3 showed gains of all 5 chromosomes and 1 had gains of chromosomes 2 and 10. The chromophobe renal cell carcinoma showed losses of chromosome 1, 6, 10, and 17. Twelve of 14 tumors from the patients with multiple oncocytomas showed no loss of any of the chromosomes 1, 2, 6, 10, or 17 and 2 had loss of chromosome 1. All the tumors from kidneys with renal oncocytosis showed strong parvalbumin immunoreactivity, whereas cytokeratin 7 and S100A1 expression were variable. In summary, the renal cell neoplasms of oncocytosis seem to have distinct morphologic, immunohistochemical, and cytogenetic profiles and likely are a distinct entity, not closely related to oncocytoma or chromophobe renal cell carcinoma.

Related: FISH Kidney Cancer


Sviatoha V, Tani E, Kleina R, et al.
Immunohistochemical analysis of the S100A1, S100B, CD44 and Bcl-2 antigens and the rate of cell proliferation assessed by Ki-67 antibody in benign and malignant melanocytic tumours.
Melanoma Res. 2010; 20(2):118-25 [PubMed] Related Publications
Malignant melanomas usually have an unfavourable prognosis and poor response to chemotherapy. Deregulation of cell proliferation, programmed cell death and intercellular interactions are among several important mechanisms that might lead to malignant transformation of melanocytes and melanoma progression. The S100A1, S100B, Bcl-2 and CD44 antigens have all been described as being involved in different processes of melanoma progression. The expression of these antigens, as well as the rate of cell proliferation, was analyzed retrospectively in melanocytic tumours from 126 patients (32 males and 94 females, age ranging from 11 to 91 years). The series included benign (45 intradermal, 27 compound and eight displastic naevi) and malignant (39 primary and 14 metastatic) melanocytic tumours. The proliferating rate assessed by Ki-67 staining was lower in naevi than in melanomas, with a correlation coefficient of r = 0814. There was no overlap for rate of proliferation between benign and malignant tumours. The expression of S100A1 was low in benign melanocytic tumours and increased in malignant melanomas (r = 0.61). In contrast, a higher percentage of S100B antigen-positive cells were observed in benign melanocytic lesions than in melanomas (Pearson correlation coefficient, 0.627). In addition, positive immunostaining for S100B antigen in malignant melanomas corresponded with the areas with increased proliferating rate. The expression of Bcl-2 was lower in melanomas than in benign melanocytic tumours (r = -0.53). Bcl-2-negative areas within melanomas had an increased proliferating rate. The expression of CD44 showed a large variation both in benign and malignant melanocytic tumours. CD44 antigen expression was higher in melanomas with known metastases than in those without metastases, but this difference was not statistically significant.

Related: MKI67 Melanoma S100B


Martin SE, Bonnin JM, Hall DC, Hattab EM
Glioblastoma with signet-ring morphology: a case report and review of the literature.
Hum Pathol. 2010; 41(3):443-6 [PubMed] Related Publications
Primary central nervous system tumors with signet-ring morphology are exceedingly rare. We report an unusual case of glioblastoma with signet-ring cell features in an 81-year-old woman. Microscopic examination revealed a highly anaplastic tumor, with a prominent proportion of tumor cells exhibiting signet-ring appearance characterized by classic round cytoplasmic inclusions and eccentrically positioned nuclei. The tumor cells were immunoreactive for glial fibrillary acidic protein and S100, and negative for cytokeratins, confirming their glial origin. Ultrastructurally, the tumor cells were noted to contain intermediate filaments, and by fluorescence in-situ hybridization analysis, they demonstrated intact 1p/19q. The presence of signet-ring cells in the central nervous system should immediately raise the suspicion of metastatic carcinoma, particularly from the upper gastrointestinal tract. In the present case, however, the morphological and immunohistochemical features were diagnostic of a malignant primary glial neoplasm (glioblastoma). This case highlights the diagnostic difficulties that can arise in such instances, given the rarity of signet-ring morphology in primary central nervous system tumors.

Related: FISH


DeRycke MS, Andersen JD, Harrington KM, et al.
S100A1 expression in ovarian and endometrial endometrioid carcinomas is a prognostic indicator of relapse-free survival.
Am J Clin Pathol. 2009; 132(6):846-56 [PubMed] Free Access to Full Article Related Publications
We sought to investigate the expression levels of S100A1 in ovarian cancer cell lines and tissues to correlate S100A1 with subtype, stage, grade, and relapse-free survival. S100A1 messenger RNA and protein were up-regulated in ovarian cancer cell lines and tumors compared with normal ovarian cell lines and tissues by gene microarray analysis, reverse transcriptase-polymerase chain reaction, quantitative reverse transcriptase-polymerase chain reaction, and Western immunoblotting. In the study, 63.7% of serous, 21.2% of clear cell, 11.2% of endometrioid, and 3% of mucinous ovarian (1/31) cancers were S100A1+ by immunohistochemical staining of tissue microarrays (n = 500). S100A1 expression increased with increasing Silverberg grade but not stage in serous tumors. Endometrial tissue microarrays (n = 127) were 9.4% S100A1+; no correlation with stage or grade and S100A1 was found. In the endometrioid subtype of ovarian and endometrial cancers, relapse-free survival was decreased for patients with S100A1+ tumors. These data suggest that S100A1 is a marker for poor prognosis of endometrioid subtypes of cancer.

Related: Endometrial (Uterus) Cancer Endometrial Cancer Ovarian Cancer


Yusenko MV, Zubakov D, Kovacs G
Gene expression profiling of chromophobe renal cell carcinomas and renal oncocytomas by Affymetrix GeneChip using pooled and individual tumours.
Int J Biol Sci. 2009; 5(6):517-27 [PubMed] Free Access to Full Article Related Publications
Due to overlapping morphology, malignant chromophobe renal cell carcinomas (RCC) and benign renal oncocytomas (RO) may pose a diagnostic problem. In the present study, we have applied different algorithms to evaluate the data sets obtained by hybridisation of pooled and also individual samples of renal cell tumours (RCT) onto two different gene expression platforms. The two approaches revealed high similarities in the gene expression profiles of chromophobe RCCs and ROs but also some differences. After identifying the differentially expressed genes by statistic analyses, the candidate genes were further selected by a real time and normal RT-PCR and their products were analysed by immunohistochemistry. We have identified CD82 and S100A1 as valuable markers for chromophobe RCC as well as AQP6 for ROs. However, these genes are expressed at the protein level in other types of RCTs as well albeit at a low frequency and low intensity. As none of the selected genes marks exclusively one type of RCTs, for the differential diagnosis of chromophobe RCCs and ROs, a set of markers such as CD82, S100A1 and AQP6 as well as some others would be an option in routine histological laboratories.

Related: CD82 Kidney Cancer


Cossu-Rocca P, Contini M, Brunelli M, et al.
S-100A1 is a reliable marker in distinguishing nephrogenic adenoma from prostatic adenocarcinoma.
Am J Surg Pathol. 2009; 33(7):1031-6 [PubMed] Related Publications
Nephrogenic adenoma is a benign lesion that may occur at any site of the genitourinary tract, usually in association with previous urothelial injuries. Although its pathogenesis is still debated, recent studies seem to confirm its derivation from renal tubular epithelium, rather than from a metaplastic process of urothelium. In addition to its uncertain origin, there can be diagnostic difficulty in distinguishing nephrogenic adenoma from prostatic adenocarcinoma, particularly with lesions arising in the prostatic urethra. So far, immunohistochemical stains are often needed to make such a distinction, and several markers have been proposed, often with controversial results. S100A1 is a calcium binding protein that has been recently reported to be expressed in renal tubular cells and in a subset of renal cell neoplasms. Alpha-methylacyl-CoA racemase (AMACR), a recently identified prostate cancer marker, has also been found to be expressed in renal tubules and in some renal epithelial neoplasms. In this study, we investigated the expression of S100A1 and AMACR in 18 nephrogenic adenomas and in 100 prostatic adenocarcinomas. A strong and distinct cytoplasmic or nucleocytoplasmic staining of S100A1 was found in 17 out of 18 cases of nephrogenic adenoma (94%), but never in prostatic adenocarcinoma. In contrast, AMACR expression was detected in 14 of 18 nephrogenic adenomas (78%) and in 96 of 100 prostatic adenocarcinomas (96%). We conclude that (1) S100A1 is a specific and sensitive immunohistochemical marker to differentiate nephrogenic adenoma from prostatic adenocarcinoma; (2) AMACR immunostaining does not seem to be a useful marker in distinguishing between these 2 lesions; (3) given that both S100A1 and AMACR have been reported to be expressed in renal tubular cells and in a subset of renal cell neoplasms, our findings confirm the histogenetic relationship between nephrogenic adenoma and renal tubular epithelium.

Related: Prostate Cancer


Kim SS, Choi YD, Jin XM, et al.
Immunohistochemical stain for cytokeratin 7, S100A1 and claudin 8 is valuable in differential diagnosis of chromophobe renal cell carcinoma from renal oncocytoma.
Histopathology. 2009; 54(5):633-5 [PubMed] Related Publications


Related: Kidney Cancer


Nonaka D, Chiriboga L, Rubin BP
Differential expression of S100 protein subtypes in malignant melanoma, and benign and malignant peripheral nerve sheath tumors.
J Cutan Pathol. 2008; 35(11):1014-9 [PubMed] Related Publications
BACKGROUND: Desmoplastic melanoma (DM) may simulate various benign and malignant lesions, including benign peripheral nerve sheath tumors (BPNSTs) and malignant peripheral nerve sheath tumors (MPNSTs). The latter case is diagnostically challenging because DM generally show only S100 protein expression but no reaction to melanocytic markers. S100 family of proteins consists of over 20 members. We report on S100 subtypes in malignant melanomas (MMs), and BPNSTs and MPNSTs to investigate differential expression.
DESIGN: S100A1, S100A2, S100A4, S100A6 and S100B immunostains were performed on 80 MMs including conventional and desmoplastic types, 86 BPNSTs and 77 MPNSTs.
RESULTS: S100A1 expression was seen in > 91% of MMs in a diffuse reaction, whereas BPNSTs showed focal or no reaction. Sixteen percent of MPNSTs focally expressed S100A1 except for one case with diffuse reaction. S100A2 staining was negative or focal in all three groups whereas S100A4 reaction was variable in all three. S100A6 was diffusely expressed in MMs, BPNSTs and MPNSTs. S100B was stained diffusely in MMs and BPNSTs, but its reaction was observed in 30% of MPNSTs in a focal fashion.
CONCLUSION: S100A1 expression was diffuse in most of MMs but absent or focal in BPNSTs and MPNSTs. This may be helpful to distinguish between the two entities.

Related: Skin Cancer


Puri PK, Forman SB, Ferringer T, Elston D
S100 A6 immunohistochemical staining for spindle cell and desmoplastic melanomas.
J Cutan Pathol. 2008; 35(2):256-7 [PubMed] Related Publications


Ning X, Sun S, Hong L, et al.
Calcyclin-binding protein inhibits proliferation, tumorigenicity, and invasion of gastric cancer.
Mol Cancer Res. 2007; 5(12):1254-62 [PubMed] Related Publications
Calcyclin-binding protein/Siah-1-interacting protein (CacyBP/SIP), a target protein of the S100 family, which includes S100A6, S100A1, S100A12, S100B, and S100P, has been identified as a component of a novel ubiquitinylation complex leading to beta-catenin degradation. However, the function of CacyBP/SIP in gastric cancer has not been elucidated. In the present study, we prepared CacyBP/SIP overexpressing and knockdown cell lines of gastric cancer. Forced CacyBP/SIP expression inhibited the proliferation of gastric cancer cells, suppressed tumorigenicity in vitro, and prolonged the survival time of tumor-bearing nude mice. In addition, increased CacyBP/SIP repressed the invasive potential of gastric cancer cells. Conversely, the down-regulation of CacyBP/SIP by RNA interference showed the opposite effects. Further studies showed that depressed CacyBP/SIP increased the expression of total and nuclear beta-catenin at the protein level and elevated the transcriptional activity of Tcf/LEF. Taken together, our results suggest that CacyBP/SIP may be a potential inhibitor of cell growth and invasion in the gastric cancer cell, at least in part through the effect on beta-catenin protein expression and transcriptional activation of Tcf/LEF.

Related: Stomach Cancer Gastric Cancer CTNNB1 gene


Yao R, Lopez-Beltran A, Maclennan GT, et al.
Expression of S100 protein family members in the pathogenesis of bladder tumors.
Anticancer Res. 2007 Sep-Oct; 27(5A):3051-8 [PubMed] Related Publications
The S100 proteins act as multifactional signaling factors that are involved in the regulation of diverse cellular processes. To explore the involvement of S100 genes in bladder cancers, S100 gene expressions were systematically evaluated at the RNA level by microarray and real-time PCR. Total RNAs were obtained from 4-hydroxybutyl(butyl)nitrosamine (OH-BBN)-induced mouse and rat bladder cancers, human bladder cancers and matched normal bladder urothelium. Microarray analysis was performed on mouse and rat bladder cancers; real-time PCR was performed in mouse, rat and human bladder cancers and their matched normal urothelium for confirmation. Microarray analysis revealed that 9 and 6 members of the S100 gene family were differentially expressed in mouse and rat bladder cancers, respectively. Thirteen members of the S100 gene family were confirmed by real-time PCR to be differentially expressed in human bladder cancers, with overexpression of S100A2, S100A3, S100A5, S100A7, S100A8, S100A9, S100A14, S100A15, S100A16 and S100P, and underexpression of S100A1, S100A4 and S100B. S100A1, S10OA3, S100A8, S10A9, S100A14, S100A15 and S100A16 showed similar patterns of differential expression in bladder cancers from mouse, rat and human. To our knowledge this is the first report of systematic evaluation of S100 gene expressions in bladder cancers. Our results indicate that differential expression of S100 gene family members is characteristic of bladder cancers and these genes may play important roles in bladder tumorigenesis and progression.

Related: Transitional Cell Cancer of the Renal Pelvis and Ureter Bladder Cancer Bladder Cancer - Molecular Biology


Tsukuda K, Hirai R, Miyake T, et al.
The outcome of gastrointestinal stromal tumors (GISTs) after a surgical resection in our institute.
Surg Today. 2007; 37(11):953-7 [PubMed] Related Publications
PURPOSE: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract arising from Cajal's cells and expressing c-kit. In a consensus report, the clinical behavior of GISTs was categorized into risk classes according to the tumor size and mitotic count. We analyzed the risk categories based on GIST patients who underwent a surgical resection at our institute during a period of 15 years.
METHODS: We evaluated the risk categories of GISTs and analyzed the outcome and risk categories retrospectively. We presented the MIB-1 score of the tumor instead of mitotic counts for the evaluation of cellular growth because of inaccuracies regarding the mitotic counts.
RESULTS: Patients were classified into 4 cases of very low risk, 11 of low risk, 8 of intermediate risk, and 5 of high risk. Four high-risk patients showed recurrence as either liver metastasis or peritoneal dissemination. In addition, local recurrence occurred in one low-risk and one intermediate-risk patient each.
CONCLUSION: Our cases confirmed the correlation between the risk categories and the prognosis. A complete resection with sufficient margin must be confirmed even in low-risk cases to prevent local recurrence. Since high-risk patients showed poor prognosis, the adjuvant treatment with chemotherapeutic regimens must therefore be further studied for high-risk patients.

Related: Gastrointestinal Stromal Tumors MKI67


Bartling B, Rehbein G, Schmitt WD, et al.
S100A2-S100P expression profile and diagnosis of non-small cell lung carcinoma: impairment by advanced tumour stages and neoadjuvant chemotherapy.
Eur J Cancer. 2007; 43(13):1935-43 [PubMed] Related Publications
Early and correct diagnosis of non-small cell lung carcinoma (NSCLC) is essential for the choice of an appropriate anti-cancer therapy. Besides the histopathological diagnosis, molecular profiling by detection of the tumour-associated gene expression might play an upcoming role. As proteins of the S100 gene family show a distinct cell type-specific expression profile, our study focused on the relevance of the S100 family for identification and classification of NSCLCs. Among the S100 members, we identified the expression of S100A1, S100A2, S100A4, S100A6, S100A9 and S100P in human lung carcinoma cells (H358(p53-), A549(p53+)) or NSCLC tissues. Distinct S100 members are increased in NSCLCs compared with control lung specimens depending on the histopathological subtype. In particular, S100A2 was upregulated in squamous cell carcinomas, whereas S100P was mainly increased in adenocarcinomas. The upregulation of either S100A2 or S100P was detected in early but less in advanced tumour stages and not at all in NSCLC patients who had received neoadjuvant chemotherapy. In conclusion, our study indicates an important role of the S100A2-S100P expression profile for molecular diagnosis of NSCLCs at early and, therefore, prognostically more favourable tumour stage. As the S100A2-S100P profile also allows the histopathological classification, it might significantly support the conventional tumour diagnostics.

Related: Non-Small Cell Lung Cancer Lung Cancer


Liang J, Luo G, Ning X, et al.
Differential expression of calcium-related genes in gastric cancer cells transfected with cellular prion protein.
Biochem Cell Biol. 2007; 85(3):375-83 [PubMed] Related Publications
The prion protein (PrPC) has a primary role in the pathogenesis of transmissible spongiform encephalopathies, which causes prion disorders partially due to Ca2+ dysregulation. In our previous work, we found that overexpressed PrPC in gastric cancer was involved in apoptosis, cell proliferation, and metastasis of gastric cancer. To better understand how PrPC acts in gastric cancer, a human microarray was performed to select differentially regulated genes that correlate with the biological function of PrPC. The microarray data were analyzed and revealed 3798 genes whose expression increased at least 2-fold in gastric cancer cells transfected with PrPC. These genes encode proteins involved in several aspects of cell biology, among which, we specially detected molecules related to calcium, especially the S100 calcium-binding proteins, and found that PrPC upregulates S100A1, S100A6, S100B, and S100P but downregulates CacyBP in gastric cancer cells. We also found that intracellular Ca2+ levels in cells transfected with PrPC increased, whereas these levels decreased in knockdowns of these cells. Taken together, PrPC might increase intracellular Ca2+, partially through calcium-binding proteins, or PrPC might upregulate the expression of S100 proteins, partially through stimulating the intracellular calcium level in gastric cancer. Though the underlying mechanisms need further exploration, this study provides a new insight into the role of PrPC in gastric cancer and enriches our knowledge of prion protein.

Related: Stomach Cancer Gastric Cancer


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Cite this page: Cotterill SJ. S100A1, Cancer Genetics Web: http://www.cancerindex.org/geneweb/S100A1.htm Accessed: date

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