Placental S100 (S100P) and GATA3: Markers for Transitional Epithelium and Urothelial Carcinoma Discovered by Complementary DNA Microarray

The morphologic distinction between prostate and urothelial carcinoma can be difficult. To identify novel diagnostic markers that may aid in the differential diagnosis of prostate versus urothelial carcinoma, we analyzed expression patterns in prostate and bladder cancer tissues using complementary DNA microarrays. Together with our prior studies on renal neoplasms and normal kidney, these studies suggested that the gene for placental S100 (S100P) is specifically expressed in benign and malignant urothelial cells. Using tissue microarrays, a polyclonal antiserum against S100P protein stained 86% of 295 urothelial carcinomas while only 3% of 260 prostatic adenocarcinomas and 1% of 133 renal cell carcinomas stained. A commercially available monoclonal antibody against S100P stained 78% of 300 urothelial carcinomas while only 2% of 256 prostatic adenocarcinomas and none of 137 renal cell carcinomas stained. A second gene, GATA3, also showed high level expression in urothelial tumors by cDNA array. A commercially available monoclonal antibody against GATA3 stained 67% of 308 urothelial carcinomas, but none of the prostate or renal carcinomas. For comparison, staining was also performed for p63 and cytokeratin 5/6. p63 stained 87% of urothelial carcinomas whereas CK5/6 stained 54%. Importantly, when S100P and p63 were combined 95% of urothelial carcinomas were labeled by one or both markers. We conclude that the detection of S100P and GATA3 protein expression may help distinguish urothelial carcinomas from other genitourinary neoplasms that enter into the differential diagnosis.

[1]  David Botstein,et al.  The Stanford Microarray Database: data access and quality assessment tools , 2003, Nucleic Acids Res..

[2]  Christian A. Rees,et al.  Systematic variation in gene expression patterns in human cancer cell lines , 2000, Nature Genetics.

[3]  Eithne Costello,et al.  Molecular alterations in pancreatic carcinoma: expression profiling shows that dysregulated expression of S100 genes is highly prevalent , 2003, The Journal of pathology.

[4]  R. Tibshirani,et al.  Gene expression profiling identifies clinically relevant subtypes of prostate cancer. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Ash A. Alizadeh,et al.  Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling , 2000, Nature.

[6]  J. Winstanley,et al.  Induction of metastasis by S100P in a rat mammary model and its association with poor survival of breast cancer patients. , 2006, Cancer research.

[7]  G. Makhatadze,et al.  Oligomerization and divalent ion binding properties of the S100P protein: a Ca2+/Mg2+-switch model. , 1998, Journal of molecular biology.

[8]  V. Gerke,et al.  S100P, a novel Ca(2+)-binding protein from human placenta. cDNA cloning, recombinant protein expression and Ca2+ binding properties. , 1992, European journal of biochemistry.

[9]  P. Kantoff,et al.  Regulation of S100P expression by androgen , 1996, The Prostate.

[10]  Yasodha Natkunam,et al.  Analysis of MUM1/IRF4 Protein Expression Using Tissue Microarrays and Immunohistochemistry , 2001, Modern Pathology.

[11]  C. Cordon-Cardo,et al.  p63 expression profiles in human normal and tumor tissues. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[12]  J. Hitomi,et al.  S100P expression in human esophageal epithelial cells: Human esophageal epithelial cells sequentially produce different S100 proteins in the process of differentiation , 2002, The Anatomical record.

[13]  D. Botstein,et al.  Cluster analysis and display of genome-wide expression patterns. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[14]  Christian A. Rees,et al.  Molecular portraits of human breast tumours , 2000, Nature.

[15]  N. Goldstein Immunophenotypic characterization of 225 prostate adenocarcinomas with intermediate or high Gleason scores. , 2002, American journal of clinical pathology.

[16]  D. Botstein,et al.  Diversity of gene expression in adenocarcinoma of the lung , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[17]  C. Langner,et al.  P63 Immunoreactivity Distinguishes Upper Urinary Tract Transitional-cell Carcinoma and Renal-cell Carcinoma Even in Poorly Differentiated Tumors , 2003, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[18]  C. Heizmann,et al.  Isolation of a YAC clone covering a cluster of nine S100 genes on human chromosome 1q21: rationale for a new nomenclature of the S100 calcium-binding protein family. , 1995, Genomics.

[19]  Kelli Montgomery,et al.  Gene expression in the normal adult human kidney assessed by complementary DNA microarray. , 2003, Molecular biology of the cell.

[20]  M Dietel,et al.  Value of p63 and cytokeratin 5/6 as immunohistochemical markers for the differential diagnosis of poorly differentiated and undifferentiated carcinomas. , 2001, American journal of clinical pathology.

[21]  R. Warnke,et al.  CD30 expression is common in mediastinal large B-cell lymphoma. , 1999, American journal of clinical pathology.

[22]  Ronald W. Davis,et al.  Quantitative Monitoring of Gene Expression Patterns with a Complementary DNA Microarray , 1995, Science.

[23]  R. Warnke,et al.  Expression of FKBP12 in Benign and Malignant Vascular Endothelium: An Immunohistochemical Study on Conventional Sections and Tissue Microarrays , 2003, The American journal of surgical pathology.

[24]  G. Makhatadze,et al.  Molecular characterization and tissue distribution of a novel member of the S100 family of EF-hand proteins. , 2001, Biochemistry.

[25]  L. Sapinoso,et al.  Functional dissection of transcriptional profiles in androgen-dependent and -independent prostate cancer , 2001, Nature Genetics.

[26]  J. Kononen,et al.  Tissue microarrays for high-throughput molecular profiling of tumor specimens , 1998, Nature Medicine.