Molecular signatures of localized clear cell renal cell carcinoma to predict disease-free survival after nephrectomy.
OBJECTIVE
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.
Klatte
Tobias
T
Department 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.
Seligson
David B
DB
LaRochelle
Jeffrey
J
Shuch
Brian
B
Said
Jonathan W
JW
Riggs
Stephen B
SB
Zomorodian
Nazy
N
Kabbinavar
Fairooz F
FF
Pantuck
Allan J
AJ
Belldegrun
Arie S
AS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002292:Carcinoma, Renal Cell / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D007680:Kidney Neoplasms / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D009392:Nephrectomy; D049451:Nomograms; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models
D014408:Biomarkers, Tumor