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Low CAIX expression and absence of VHL gene mutation are associated with tumor aggressiveness and poor survival of clear cell renal cell carcinoma.

Authors
  • Patard, Jean-Jacques
  • Fergelot, Patricia
  • Karakiewicz, Pierre I
  • Klatte, Tobias
  • Trinh, Quoc-Dien
  • Rioux-Leclercq, Nathalie
  • Said, Jonathan W
  • Belldegrun, Arie S
  • Pantuck, Allan J
Type
Published Article
Journal
International Journal of Cancer
Publisher
Wiley (John Wiley & Sons)
Publication Date
Jul 15, 2008
Volume
123
Issue
2
Pages
395–400
Identifiers
DOI: 10.1002/ijc.23496
PMID: 18464292
Source
Medline
License
Unknown

Abstract

We attempted to describe, in a series of clear cell renal cell carcinoma (RCC), the relationship between CAIX expression, VHL gene mutations, tumor characteristics and outcome. Radical nephrectomy was performed in 100 patients. Genomic DNA was extracted from frozen tumor samples. Four amplimers covering the whole coding sequence of the VHL gene were synthesized by PCR and sequenced. The monoclonal antibody M75 was used to evaluate CAIX protein expression immunohistochemically. VHL mutations were identified in 58 patients (58%) and high CAIX expression (>85%) was observed in 78 (78%). Tumors with VHL mutation showed higher CAIX expression than those without (p = 0.02). Low CAIX expression and absence of VHL mutation were associated with a more advanced tumors e.g., higher T stages and presence of metastases. VHL mutation and high CAIX expression predicted longer progression-free survival (p = 0.037) and disease-specific survival (p = 0.001), respectively. In combination, they defined three prognostic groups (p = 0.002): (i) good prognosis, defined as VHL mutation and high CAIX (2-year survival: 86%), (ii) intermediate prognosis with either VHL mutation or high CAIX (69%), and (iii) poor prognosis with no VHL mutation and low CAIX (45%, median survival 18 months). CAIX expression, but not VHL mutational status, was an independent prognostic factor in multivariate analysis. Taken together, CAIX expression and VHL mutational status are able to stratify patients with clear cell RCC into distinct groups with regards to clinicopathological variables and prognosis, with low CAIX expression and absence of VHL mutation being associated with a poor clinicopathological phenotype and diminished survival.

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