Loss of p16 expression is of prognostic significance in locally advanced prostate cancer: an analysis from the Radiation Therapy Oncology Group protocol 86-10.
OBJECTIVE
The retinoblastoma (RB) cell cycle regulatory pathway is known to be deregulated in virtually all known human tumors. The protein product of the RB gene, pRB, and its upstream regulator, p16, are among the most commonly affected members of this pathway. We investigated the prognostic significance of both pRB and p16 expression in locally advanced prostate cancers, from patients treated on the Radiation Therapy Oncology Group (RTOG) protocol 86-10.


METHODS
Sixty-seven cases from RTOG 86-10 had immunohistochemically stained slides, judged interpretable for both p16 and pRB, available for analysis. Median follow-up was 8.9 years (range, 6.0 to 11.8 years) for surviving patients. Staining for each marker was then correlated with overall survival, local progression, distant metastasis, and disease-specific survival.


RESULTS
Loss of p16 expression, as defined by expression was significantly associated with reduced overall survival (P =.039), disease-specific survival (P =.006), and higher risk of local progression (P =.0007) and distant metastasis (P =.026) in the univariate analysis. In the multivariate analysis, loss of p16 was significantly associated with reduced disease-specific survival (P =.0078) and increased risk of local failure (P =.0035) and distant metastasis (P =.026). A borderline association with reduced overall survival (P =.07) was also evident. Loss of pRB was associated with improved disease-specific survival on univariate (P =.028) and multivariate analysis (P =.043), but carried no other significant outcome associations.


CONCLUSIONS
Loss of p16 is significantly associated with adverse clinical outcome in cases of locally advanced prostate cancer.
Chakravarti
A
A
Radiation Therapy Oncology Group Genitourinary Translational Research Program. achakravarti@partners.org.
Heydon
K
K
Wu
C L
CL
Hammond
E
E
Pollack
A
A
Roach
M
M
Wolkov
H
H
Okunieff
P
P
Cox
J
J
Fontanesi
J
J
Abrams
R
R
Pilepich
M
M
Shipley
W
W
D000328:Adult; D000368:Aged; D016009:Chi-Square Distribution; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D018450:Disease Progression; D018572:Disease-Free Survival; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D016019:Survival Analysis
D019941:Cyclin-Dependent Kinase Inhibitor p16