Loss of p16 expression is of prognostic significance in locally advanced prostate cancer: An analysis from the Radiation Therapy Oncology Group protocol 86-10

Purpose: 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 p 16 expression in locally advanced prostate cancers, from patients treated on the Radiation Therapy Oncology Group (RTOG) protocol 86-10. Materials and Methods: Sixty-seven cases from RTOG 86-10 had immunohistochemically stained slides, judged interpretable for both p 16 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 p 16 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. Conclusion: Loss of p16 is significantly associated with adverse clinical outcome in cases of locally advanced prostate cancer. (C) 2003 by American Society of Clinical Oncology.