P53 AND BCL-2 IMMUNOHISTOCHEMICAL ALTERATIONS IN PROSTATE-CANCER TREATED WITH RADIATION-THERAPY

Objectives. Radiation therapy is definitive treatment for localized pr ostate cancer. It causes cellular deoxyribonucleic acid (DNA) damage, which, if irreparable, results in apoptosis or programmed cell death. Overexpression of mutant p53 and/or bcl-2 proteins prolongs cell survi val despite exposure to damaging agents. We examined whether abnormal expression of either gene could help to explain radiation therapy fail ures in prostate cancer. Methods. Archival tissue from patients who ha d failed radiation therapy as treatment for prostate cancer was obtain ed before and after treatment. These cancer samples were examined immu nohistochemically for accumulation of p53 and bcl-2 proteins. Comparis on was made with specimens from patients who had no evidence of recurr ent or persistent disease at least 3 years following radiation therapy . Results. High rates of p53 immunopositivity were found in the prosta te tissue from all groups studied. More patients who had failed radiat ion therapy were found to have bcl-2 immunopositive specimens than wer e those without evidence for recurrent disease (41% preradiation and 6 1% postradiation versus 8%, P <0.05). More patients who failed radiati on therapy had both p53 and bcl-2 immunopositive prostate tissue than did those who were treated successfully (32% preradiation and 48% post radiation versus 8%). Conclusions. bcl-2 immunopositivity, with or wit hout concomitant detection of p53, was found in significantly more can cers of patients who failed radiation therapy. Positive staining for b cl-2 may serve as a marker for determining the radiation sensitivity o f a tumor and thus may help to guide treatment options. It is also not able that a high proportion of the prostate cancers examined were immu nopositive for p53. (C) 1998, Elsevier Science Inc. All rights reserve d.