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Cancer Epidemiol Biomarkers Prev. 2009 Mar;18(3):894-900. doi: 10.1158/1055-9965.EPI-08-0786. Epub 2009 Feb 24.

Molecular signatures of localized clear cell renal cell carcinoma to predict disease-free survival after nephrectomy.

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  • 1Department of Urology, David Geffen School of Medicine, University of California-Los Angeles, 10833 Le Conte Avenue, 66-118 CHS, Box 951738, Los Angeles, CA 90095-1738, USA.

Abstract

PURPOSE:

To identify the molecular signature of localized (N0M0) clear cell renal cell carcinoma (RCC) and assess its ability to predict outcome.

METHODS:

Clinical characteristics and pathologic records of 170 patients with localized clear cell RCC who underwent nephrectomy were reviewed. Immunohistochemical analysis was done on a tissue microarray of all primary tumors using a kidney cancer-related panel of protein markers, which included CAIX, CAXII, CXCR3, gelsolin, Ki-67, vimentin, EpCAM, p21, p27, p53, pS6, PTEN, HIF-1alpha, pAkt, VEGF-A, VEGF-C, VEGF-D, VEGFR-1, VEGFR-2, and VEGFR-3. Associations with disease-free survival (DFS) were evaluated with Cox models, and a concordance index assessed prognostic accuracy.

RESULTS:

Median follow-up was 7.1 years. The final multivariate Cox model determined T classification, Eastern Cooperative Oncology Group performance status, and five molecular markers (Ki-67, p53, endothelial VEGFR-1, epithelial VEGFR-1, and epithelial VEGF-D) to be independent prognostic indicators of DFS. The molecular signature based on these markers predicted DFS with an accuracy of 0.838, an improvement over T classification of 0.746, and the University of California-Los Angeles Integrated Staging System of 0.780. A constructed nomogram combined the molecular, clinical, and pathologic factors and approached a concordance index of 0.904.

CONCLUSIONS:

A molecular signature consisting of five molecular markers (Ki-67, p53, endothelial VEGFR-1, epithelial VEGFR-1, and epithelial VEGF-D) can predict DFS for localized clear cell RCC. The prognostic ability of the signature and nomogram may be superior to clinical and pathologic factors alone and may identify a subset of localized patients with aggressive clinical behavior. Independent, external validation of the nomogram is required.

PMID:
19240241
[PubMed - indexed for MEDLINE]
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