PT  - JOURNAL ARTICLE
AU  - Klatte, Tobias
AU  - Seligson, David B.
AU  - LaRochelle, Jeffrey
AU  - Shuch, Brian
AU  - Said, Jonathan W.
AU  - Riggs, Stephen B.
AU  - Zomorodian, Nazy
AU  - Kabbinavar, Fairooz F.
AU  - Pantuck, Allan J.
AU  - Belldegrun, Arie S.
TI  - Molecular Signatures of Localized Clear Cell Renal Cell Carcinoma to Predict Disease-Free Survival after Nephrectomy
AID  - 10.1158/1055-9965.EPI-08-0786
DP  - 2009 Mar 01
TA  - Cancer Epidemiology Biomarkers & Prevention
PG  - 894--900
VI  - 18
IP  - 3
4099  - http://cebp.aacrjournals.org/content/18/3/894.short
4100  - http://cebp.aacrjournals.org/content/18/3/894.full
SO  - Cancer Epidemiol Biomarkers Prev2009 Mar 01; 18
AB  - 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-1α, 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. (Cancer Epidemiol Biomarkers Prev 2009;18(3):894–900)