Received 28 October 2008 published online 18 June 2009.
Refers to article:
Prognostic Implications of Polymorphisms and Interleukin-2 Therapy for Renal Cell Carcinoma
, 15 June 2009
Thomas A. Gardner, Theodore Logan
The Journal of Urology
August 2009 (Vol. 182, Issue 2, Pages 425-426) Full Text |
Full-Text PDF (101 KB)
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.
aDepartment of Urology, University of California-Los Angeles, Los Angeles, California
bDepartment of Pathology and Laboratory Medicine, University of California-Los Angeles, Los Angeles, California
cDepartment of Medicine, University of California-Los Angeles, Los Angeles, California
Correspondence: Division of Urologic Oncology, Department of Urology, University of California-Los Angeles, 650 Charles East Young Dr., Los Angeles, California 90095-1738 (telephone: 310-206-1434; FAX: 310-206-5343)
Study received institutional review board approval.
ABSTRACT