Expression of the proapoptotic protein Bid is an adverse prognostic factor for radiotherapy outcome in carcinoma of the cervix.
The Bcl-2 family of apoptotic regulators is thought to play an essential role in cancer development and influence the sensitivity of tumour cells to radiotherapy. Bid is an abundantly expressed Bcl-2 family protein playing a central role in various pathways of apoptosis by integrating and converging signals at the mitochondria. The relevance of apoptotic modulation by Bcl-2 and related proteins in tumour development and radiation response for human tumours remains undefined. Therefore, a study was made regarding the expression of Bid in patients with locally advanced cervix carcinoma who received radiotherapy. Bid expression was assessed using immunohistochemistry in pretreatment archival biopsies from 98 patients. The data were correlated with clinicopathologic characteristics and treatment outcome. Pretreatment tumour radiosensitivity data were available for 60 patients. Strong Bid expression was associated with a patient age less than the median of 52 years (P=0.034) and poor metastasis-free survival. In multivariate analysis, after allowing for stage, Bid expression was a significant prognostic factor for both disease-specific and metastasis-free survival (P=0.026). It is concluded that strong tumour Bid expression is associated with poor outcome following radiotherapy regardless of intrinsic tumour cell radiosensitivity, and is adverse prognostic for disease-specific and metastasis-free survival in younger patients.
Green
M M L
MM
Experimental Oncology Group, School of Pharmacy and Pharmaceutical Sciences, Coupland III, University of Manchester, Oxford Road, Manchester M13 9PL, UK.
Hutchison
G J
GJ
Valentine
H R
HR
Fitzmaurice
R J
RJ
Davidson
S E
SE
Hunter
R D
RD
Dive
C
C
West
C M L
CM
Stratford
I J
IJ
D017209:Apoptosis; D051023:BH3 Interacting Domain Death Agonist Protein; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000532:radiotherapy*; D002352:Carrier Proteins / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000532:radiotherapy*
D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D002352:Carrier Proteins; D019253:Proto-Oncogene Proteins c-bcl-2