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

Tobias Klatte, David B. Seligson, Jeffrey LaRochelle, Brian Shuch, Jonathan W. Said, Stephen B. Riggs, Nazy Zomorodian, Fairooz F. Kabbinavar, Allan J. Pantuck, Arie S. Belldegrun

Research output: Contribution to journalArticle

129 Scopus citations

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-1A, 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.

Original languageEnglish (US)
Pages (from-to)894-900
Number of pages7
JournalCancer Epidemiology Biomarkers and Prevention
Volume18
Issue number3
DOIs
StatePublished - Mar 2009

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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    Klatte, T., Seligson, D. B., LaRochelle, J., Shuch, B., Said, J. W., Riggs, S. B., Zomorodian, N., Kabbinavar, F. F., Pantuck, A. J., & Belldegrun, A. S. (2009). Molecular signatures of localized clear cell renal cell carcinoma to predict disease-free survival after nephrectomy. Cancer Epidemiology Biomarkers and Prevention, 18(3), 894-900. https://doi.org/10.1158/1055-9965.EPI-08-0786