The Prognostic Value of p16 Expression in Locally Advanced Prostate Cancer: A Study Based on RTOG 92-02

Chakravarti, Arnab; DeSilvio, Michelle; Zhang, M.; Grignon, David J.; Rosenthal, Seth A.; Asbell, S.; Hanks, Gerald E.; Sandler, Howard M.; Pollack, Alan; Zhai, Gary; Shipley, W.

doi:10.1016/j.ijrobp.2005.07.036

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“…The data suggest that men with tumors overexpressing Bcl-2 and/or altered Bax expression should receive LTAD+RT as opposed to STAD+RT. The RTOG translational research group has been investigating a series of potential biomarkers in tissue from patients in protocol 92-02 including Ki-67, p53, MDM2, p16 (16,36,37), and now Bcl-2 and Bax. The aim is to ultimately establish a consensus biomarker panel for risk stratification of high-risk prostate cancer patients.…”

Section: Discussionmentioning

confidence: 99%

Bcl-2 and Bax Expression Predict Prostate Cancer Outcome in Men Treated with Androgen Deprivation and Radiotherapy on Radiation Therapy Oncology Group Protocol 92-02

Khor

Moughan

Al‐Saleem

et al. 2007

Clinical Cancer Research

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Purpose: Bcl-2 is antiapoptotic, and its overexpression has been associated with resistance to androgen deprivation and poor outcome in some patients treated with radiotherapy. Bax is proapoptotic, regulating Bcl-2 through heterodimer formation. In a prior study, Bcl-2 and Bax were not related to outcome in locally advanced patients treated with radiotherapy or short-term androgen deprivation + radiotherapy (STAD+RT) on another RadiationTherapy Oncology Group trial (86-10). A follow-up investigation was carried out here in more contemporary high-risk men treated on Radiation Therapy Oncology Group 92-02 with STAD+RT or long-term AD+RT (LTAD+RT). Experimental Design: Adequate tissue was available to be analyzed immunohistochemically in 502 patients for Bcl-2 and 343 patients for Bax. Univariate and multivariate analyses by Cox proportional hazards models were applied to end points of failure. Results: Bcl-2 was positive in 45.6% cases, and Bax expression altered in 53.9% cases. Abnormal Bcl-2 was not related to any of the failure end points tested. Altered Bax expression was significantly associated with any failure (P = 0.023) and marginally with biochemical failure (P = 0.085). The combination of negative Bcl-2/normal Bax expression seemed more robust, being significantly related to reduced biochemical failure (P = 0.036) and any failure (P = 0.046). The predictive value of negative Bcl-2/normal Bax was most pronounced in those who received STAD+RT, as opposed to LTAD+RT. Conclusions: Normal Bax expression was associated with significantly more favorable outcome. The combination of negative Bcl-2 and normal Bax was more consistently significant, particularly when STAD+RT was the treatment administered. These data suggest that LTAD+RT should be used when either Bcl-2 or Bax is abnormally expressed.

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Section: Discussionmentioning

confidence: 99%