CA9 Gene: Single Nucleotide Polymorphism Predicts Metastatic Renal Cell Carcinoma Prognosis

Michela de Martino, Tobias Klatte, David B. Seligson, Jeffrey LaRochelle, Brian Shuch, Randy Caliliw, Zhenhua Li, Fairooz F. Kabbinavar, Allan J. Pantuck, Arie S. Belldegrun

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Purpose: We assessed CA9 single nucleotide polymorphisms and mutations, and their association with CAIX protein expression, overall survival and response to interleukin-2 in white patients with metastatic clear cell renal cell carcinoma. Materials Methods: Genomic DNA was extracted from frozen tumor samples of 54 metastatic clear cell renal cell carcinomas. The CA9 gene exons and flanking regions were amplified by polymerase chain reaction and sequenced. The monoclonal antibody M75 was used to evaluate CAIX protein expression in the primary tumor by immunohistochemistry. Results: CA9 reference single nucleotide polymorphisms rs2071676, rs12553173, rs3829078 and rs1048638 were found in 59%, 15%, 11% and 33% of patients, respectively. The deletion c.376del393 was observed in 2 patients. CAIX expression was greater than 85% in 65% of patients. No single nucleotide polymorphisms were significantly associated with CAIX expression. Patients with the C allele variant of rs12553173 had improved median survival (27.3 vs 13.6 months, p = 0.0431) and a greater likelihood of an interleukin-2 response (57% vs 22%, p = 0.081) Likewise high CAIX expression was associated with longer median survival (25.5 vs 8.5 months, p <0.0001) and a greater interleukin-2 response rate (37% vs 8%, p = 0.070). In a multivariate Cox model the C allele variant of CA9 single nucleotide polymorphism rs12553173 and CAIX expression were retained as independent prognostic factors. Conclusions: CA9 single nucleotide polymorphisms are common in patients with metastatic clear cell renal cell carcinoma. The synonymous C allele variant of rs12553173 may be associated with improved overall survival and a greater likelihood of a response to interleukin-2. CA9 rs12553173 and CAIX are independent prognostic factors of overall survival and complementary for predicting the prognosis of metastatic clear cell renal cell carcinoma.

Original languageEnglish (US)
Pages (from-to)728-734
Number of pages7
JournalJournal of Urology
Volume182
Issue number2
DOIs
StatePublished - Aug 2009

Keywords

  • CA9 protein
  • carcinoma
  • human
  • kidney
  • neoplasm metastasis
  • polymorphism
  • renal cell
  • single nucleotide

ASJC Scopus subject areas

  • Urology

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