title: 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.
abstract: OBJECTIVE
  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 Radiation Therapy 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).
  
  
  METHODS
  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.
authors.affiliation: Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
authors.forename: Li Yan
authors.initials: LY
authors.lastname: Khor
authors.forename: Jennifer
authors.initials: J
authors.lastname: Moughan
authors.forename: Tahseen
authors.initials: T
authors.lastname: Al-Saleem
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Hammond
authors.forename: Varagur
authors.initials: V
authors.lastname: Venkatesan
authors.forename: Seth A
authors.initials: SA
authors.lastname: Rosenthal
authors.forename: Mark A
authors.initials: MA
authors.lastname: Ritter
authors.forename: Howard M
authors.initials: HM
authors.lastname: Sandler
authors.forename: Gerald E
authors.initials: GE
authors.lastname: Hanks
authors.forename: William U
authors.initials: WU
authors.lastname: Shipley
authors.forename: Alan
authors.initials: A
authors.lastname: Pollack
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D011878:Radiotherapy; D016896:Treatment Outcome; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis*
chemical_list: D000726:Androgen Antagonists; D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein