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Ann Oncol. 2013 Feb;24(2):343-9. doi: 10.1093/annonc/mds463. Epub 2012 Sep 28.

c-Met is a prognostic marker and potential therapeutic target in clear cell renal cell carcinoma.

Author information

1
Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA. geoffrey.gibney@moffitt.org

Abstract

BACKGROUND:

Activation of the c-Met pathway occurs in a range of malignancies, including papillary renal cell carcinoma (RCC). Its activity in clear cell RCC is less clear. We investigated c-Met expression and inhibition in a large cohort of RCC tumors and cell lines.

METHODS:

c-Met protein expression was determined by automated quantitative analysis (AQUA) on a tissue microarray (TMA) constructed from 330 RCC tumors paired with adjacent normal renal tissue. c-Met expression and selective inhibition with SU11274 and ARQ 197 were studied in clear cell RCC cell lines.

RESULTS:

Higher c-Met expression was detected in all RCC subtypes than in the adjacent normal renal tissue (P < 0.0001). Expression was highest in papillary and sarcomatoid subtypes, and high-grade and stage tumors. Higher c-Met expression correlated with worse disease-specific survival [risk ratio = 1.36; 95% confidence interval (CI) 1.08-1.74; P = 0.0091] and was an independent predictor of survival, maintained in clear cell subset analyses. c-Met protein was activated in all cell lines, and proliferation (and colony formation) was blocked by SU11274 and ARQ 197.

CONCLUSIONS:

c-Met is associated with poor pathologic features and prognosis in RCC. c-Met inhibition demonstrates in vitro activity against clear cell RCC. Further study of ARQ 197 with appropriate biomarker studies in RCC is warranted.

PMID:
23022995
PMCID:
PMC3551486
DOI:
10.1093/annonc/mds463
[Indexed for MEDLINE]
Free PMC Article
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