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CA9 gene: Single nucleotide polymorphism predicts metastatic renal cell carcinoma prognosis
The Journal of Urology, 07/23/09

de Martino M et al. – Study reports that CA9 single nucleotide polymorphisms (SNPs) are common in patients with metastatic clear cell renal cell carcinoma (RCC). The synonymous C allele variant of rs12553173 may be associated with improved overall survival and a greater likelihood of a response to IL-2. CA9 rs12553173 and CAIX are independent prognostic factors of overall survival and complementary for predicting the prognosis.

Methods

Main objectives of this study were to:
- Assess CA9 SNPs and mutations, and
- Their association with CAIX protein expression, overall survival and response to IL-2
  in white patients with metastatic clear cell RCC
Genomic DNA was extracted from 54 frozen tumor samples
CA9 gene exons and flanking regions were amplified by PCR and sequenced
Monoclonal Ab M75 was used to evaluate CAIX protein expression in the primary tumor by IHC

Results

CA9 reference SNPs rs2071676, rs12553173, rs3829078 and rs1048638 were found in 59%, 15%, 11% and 33% of pts, respectively
The deletion c.376del393 was observed in 2 pts
CAIX expression was greater than 85% in 65% of pts
No SNPs were associated with CAIX expression
Pts with the C allele variant of rs12553173 had improved median survival and a greater likelihood of an IL-2 response
Likewise high CAIX expression was associated with longer median survival and a greater IL-2 response rate
C allele variant of CA9 SNP rs12553173 and CAIX expression were independent prognostic factors

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