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CA9 gene: single nucleotide polymorphism predicts metastatic renal cell carcinoma prognosis.

AbstractPURPOSE:
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.
AuthorsMichela de Martino, Tobias Klatte, David B Seligson, Jeffrey LaRochelle, Brian Shuch, Randy Caliliw, Zhenhua Li, Fairooz F Kabbinavar, Allan J Pantuck, Arie S Belldegrun
JournalThe Journal of urology (J Urol) Vol. 182 Issue 2 Pg. 728-34 (Aug 2009) ISSN: 1527-3792 [Electronic] United States
PMID19539328 (Publication Type: Journal Article)
Chemical References
  • Antigens, Neoplasm
  • Antineoplastic Agents
  • Interleukin-2
  • CA9 protein, human
  • Carbonic Anhydrases
Topics
  • Adult
  • Aged
  • Antigens, Neoplasm (genetics)
  • Antineoplastic Agents (therapeutic use)
  • Carbonic Anhydrases (genetics)
  • Carcinoma, Renal Cell (drug therapy, genetics, mortality, secondary)
  • Female
  • Humans
  • Interleukin-2 (therapeutic use)
  • Kidney Neoplasms (drug therapy, genetics, mortality, pathology)
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Survival Rate

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