Significant variation of immunohistochemical marker expression in paired primary and metastatic clear cell renal cell carcinomas

Am J Clin Pathol. 2013 Sep;140(3):410-8. doi: 10.1309/AJCP8DMPEIMVH6YP.

Abstract

Objectives: To compare the immunohistochemical expression of diagnostic markers in primary clear cell renal cell carcinomas (RCCs) and their matched metastases.

Methods: Tissue microarrays were constructed from 15 pairs of primary and metastatic clear cell RCCs and then evaluated for the immunohistochemical expression of renal cell carcinoma antigen (RCCA), kidney-specific cadherin, carbonic anhydrase IX (CAIX), and paired box genes 2 (PAX2) and 8 (PAX8).

Results: There was significantly higher overall marker expression in metastatic tumors compared to their matched primaries (P < .001). Individually, there was greater CAIX, PAX2, and PAX8 expression and lower RCCA expression in metastatic tumors. Most importantly, a significant proportion of originally RCCA-positive tumors lost such expression in metastases.

Conclusions: Metastatic RCCs have significantly higher expression of PAX2 and PAX8 compared to primary RCCs. RCCA is not very reliable in this diagnostic setting, both because of its lower overall sensitivity and loss of expression in metastatic RCCs.

Keywords: Carbonic anhydrase IX; Immunohistochemistry; Kidney-specific cadherin; Metastatic clear cell renal cell carcinoma; Paired box gene 2; Paired box gene 8; RCC antigen; Renal markers.

MeSH terms

  • Antigens, Neoplasm
  • Biomarkers, Tumor / metabolism
  • Cadherins / metabolism
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases / metabolism
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / pathology
  • Carcinoma, Renal Cell / secondary
  • Humans
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology
  • PAX2 Transcription Factor / metabolism
  • PAX8 Transcription Factor
  • Paired Box Transcription Factors / metabolism
  • Receptor for Advanced Glycation End Products / metabolism

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Cadherins
  • PAX2 Transcription Factor
  • PAX2 protein, human
  • PAX8 Transcription Factor
  • PAX8 protein, human
  • Paired Box Transcription Factors
  • Receptor for Advanced Glycation End Products
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases