Bax and Bcl-2 expressions predict response to radiotherapy in human cervical cancer.
OBJECTIVE
The ratio of Bcl-2 to Bax expression determines survival or death following an apoptotic stimulus. In order to establish a new predictor of the outcome of treatment for human cervical carcinoma, we investigated the relationship between the expressions of the Bax and Bcl-2 proteins and the response to radiotherapy after the administration of 10.8 Gy.


METHODS
A total of 44 patients with histologically proven carcinoma of the uterine cervix, including three with recurrent cervical stump carcinomas, were treated with definitive radiotherapy. The presence of mutations in exons 5-8 of the p53 gene was analyzed by a single-strand conformation polymorphism analysis and DNA sequencing.


RESULTS
Forty patients were found to have wild-type p53, and the remaining four had mutant p53. The Bax and Bcl-2 protein expressions prior to radiotherapy did not correlate with response and survival. However, the Bax and Bcl-2 protein expressions after radiotherapy correlated with both response and survival. Bax-positive tumors showed significantly better responses than the Bax-negative tumors after 10.8 Gy radiation (P = 0.0002). In contrast, the Bcl-2-positive tumors showed significantly poorer responses than the Bcl-2-negative tumors after radiation (P = 0.002). Increased Bax expression after the 10.8 Gy radiotherapy was found to be correlated with good survival (P = 0.04). In contrast, increased Bcl-2 expression after such radiotherapy was correlated with poor survival (P = 0.002).


CONCLUSIONS
The levels of Bax and Bcl-2 expression after 10.8 Gy radiotherapy are useful prognostic markers in patients with human cervical carcinoma.
Harima
Y
Y
Department of Radiology, Kansai Medical University, Moriguchi City, Osaka, Japan. harima@takii.kmu.ac.jp
Harima
K
K
Shikata
N
N
Oka
A
A
Ohnishi
T
T
Tanaka
Y
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000528:radiation effects*; D017931:DNA Primers; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000528:radiation effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000528:radiation effects*; D016019:Survival Analysis; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000528:radiation effects*; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D014408:Biomarkers, Tumor; D017931:DNA Primers; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein