RGD Reference Report - 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. - Rat Genome Database

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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.

Authors: Khor, LY  Moughan, J  Al-Saleem, T  Hammond, EH  Venkatesan, V  Rosenthal, SA  Ritter, MA  Sandler, HM  Hanks, GE  Shipley, WU  Pollack, A 
Citation: Khor LY, etal., Clin Cancer Res. 2007 Jun 15;13(12):3585-90.
RGD ID: 1643354
Pubmed: PMID:17575222   (View Abstract at PubMed)
PMCID: PMC2763095   (View Article at PubMed Central)
DOI: DOI:10.1158/1078-0432.CCR-06-2972   (Journal Full-text)

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 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). 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
prostate cancer  IEP 1643354 RGD 
prostate cancer  ISOBAX (Homo sapiens)1643354; 1643354 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Bax  (BCL2 associated X, apoptosis regulator)

Genes (Mus musculus)
Bax  (BCL2-associated X protein)

Genes (Homo sapiens)
BAX  (BCL2 associated X, apoptosis regulator)


Additional Information