Prognostic value of carbonic anhydrase IX and KI67 as predictors of survival for renal clear cell carcinoma.
OBJECTIVE
The natural history of renal cell carcinoma (RCC) is complex and not entirely explained by conventional prognostic factors. In this study we evaluated the prognostic value of carbonic anhydrase IX (CAIX) and Ki67 to predict survival in RCC.


METHODS
Immunohistochemical analysis using a CAIX and a Ki67 monoclonal antibody was performed on tissue microarrays constructed from paraffin embedded specimens from 224 patients treated with nephrectomy for clear cell renal carcinoma. CAIX and Ki67 staining were correlated with clinical factors, pathological features and survival. Median followup was 34 months (range 0.3 to 117) and disease specific survival was the primary end point assessed.


RESULTS
Univariate statistical analysis showed that high Ki67 staining and low CAIX staining correlated significantly with poor median survival (21 months, p < 0.001 and 22 months, p = 0.011, respectively). Each marker was highly significant for stratifying patient groups defined by T stage, Fuhrman grade, nodal status, metastatic status and performance status. On multivariate analysis CAIX and Ki67 were significant predictors of survival with an HR of 1.78 (p = 0.014) and 1.75 (p = 0.009), respectively. Although CAIX and Ki67 staining were inversely correlated (p = 0.009), Ki67 significantly substratified patient subgroups defined by high or low CAIX staining (p = 0.001 and 0.003, respectively). When Ki67 and CAIX were combined into a single parameter, RCC tumors could be stratified into low, intermediate and high risk groups with a median survival of greater than 101, 31 and 9 months, respectively (p <0.001). On multivariate analysis the combined parameter consisting of Ki67 and CAIX was a significant predictor of survival (p <0.001) and it was able to displace histological grade.


CONCLUSIONS
Ki67and CAIX are useful prognostic biomarkers for RCC that improve the survival prediction and classification of kidney cancer.
Bui
Matthew H T
MH
Departments of Urology, University of California-Los Angeles, California 90095-1738, USA.
Visapaa
Harri
H
Seligson
David
D
Kim
Hyung
H
Han
Ken-Ryu
KR
Huang
Yunda
Y
Horvath
Steve
S
Stanbridge
Eric J
EJ
Palotie
Aarno
A
Figlin
Robert A
RA
Belldegrun
Arie S
AS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000032:analysis / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000096:biosynthesis*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000032:analysis / Q000096:biosynthesis*; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000401:mortality*; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis / Q000096:biosynthesis*; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D015996:Survival Rate
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases