Expression of S-100 protein in renal cell neoplasms

Fan Lin*, Wannian Yang, Mark Betten, Bin Tean Teh, Ximing J. Yang, Stephane Richard, Sophie Giraud, Sophie Ferlicot, Philippe Vielh, Delphine Amsellem-Ouazana, Bernard Debré, Thierry Flam, Nicolas Thiounn, Marc Zerbib, Gérard Benoît, Stéphane Droupy, Vincent Molinié, Annick Vieillefond

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


Polyclonal antibody to S-100 protein has been routinely applied for initial screening of various types of tumors, including, melanocytic tumors and neurogenic tumors. S-100 protein has been shown to have a broad distribution in human tissues, including renal tubules. The potential utility of S-100 protein in renal cell neoplasms has not been extensively investigated. Using an EnVision-Horseradish Peroxidase (HRP; Dako, Carpinteria, Calif) kit, we evaluated the diagnostic value of S-100 protein on tissue microarray sections from 175 cases of renal epithelial neoplasm (145 primary renal neoplasms and 30 metastatic renal cell carcinomas) and 24 non-neoplastic renal tissues. Immunohistochemical stains for pancytokeratin, HMB-45, and Mart-1 were also performed. Western blot using the same antibody (anti-S-100 protein) was performed on 10 cases of renal cell neoplasm. The results demonstrated that nuclear and cytoplasmic staining pattern for S-100 protein was observed in 56 (69%) of 81 conventional (clear cell) renal cell carcinomas (RCCs), 10 (30%) of 33 papillary RCCs, 1 (6%) of 16 ChRCCs, and 13 (87%) of 15 oncocytomas. Among the 81 cases of CRCC, positivity for S-100 protein was seen in 41 (71%) of 58 and 15 (65%) of 23 cases with Furhman nuclear grade I/II and III/IV, respectively. Focal immunostaining was present in 22 (92%) of 24 normal renal tubules. Similar staining pattern was observed in 21 (70%) of 30 metastatic RCCs. Western blotting demonstrated the S-100 protein expression in both renal cell neoplasm and normal renal tissue. Overexpression of S-100 in oncocytomas compared with ChRCCs was confirmed by the data of Western blot and cDNA microarray analysis. Importantly, 14.8% (12/81) of clear cell RCC and 13.3% (4/30) of metastatic RCC revealed an immunostaining profile of pancytokeratin (-)/S-100 protein (+). These data indicate that caution should be taken in interpreting an unknown primary with S-100 positivity and cytokeratin negativity. In addition, it suggests that S-100 has a diagnostic value in differentiating oncocytoma from RCC.

Original languageEnglish (US)
Pages (from-to)462-470
Number of pages9
JournalHuman pathology
Issue number4
StatePublished - Apr 2006


  • Chromophobe renal cell carcinoma
  • Metastatic renal cell carcinoma
  • Oncocytoma
  • Pancytokeratin
  • Primary renal cell carcinoma
  • S-100 protein

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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