bcl-2 immunoreactivity but not p53 accumulation associated with tumour response to radiotherapy in cervical carcinoma.
OBJECTIVE
This study seeks to define the role of pretreatment expression of the tumour-suppressor p53 protein and the anti-apoptotic protein bcl-2 and their relationship to tumour response to radiotherapy in cervical carcinoma.


METHODS
A total of 101 patients were evaluated and the possibility of a correlation done between the pretreatment status of the two proteins and clinical outcome following radiotherapy was investigated. Such patients were either disease-free (group 1, n = 65) or had residual/recurrent disease (group 2, n = 36) at a 16-month follow-up. p53 and bcl-2 protein expression was determined by immunocytochemistry. The presence of mutant p53 was detected by a mutant specific p53 enzyme-linked immunosorbent assay.


RESULTS
There was no correlation between p53 immunoreactivity or the presence of mutant p53 protein and disease status after treatment. Expression of bcl-2 protein, however, showed significant pretreatment correlations with the final disease outcome (r = 0.643, P = 0.0001). Moreover the odds ratio of a tumour expressing moderate to intense levels of bcl-2 responding poorly to radiotherapy was 27.2 (95% CI 6.0, 123.3).


CONCLUSIONS
bcl-2 protein functions in an anti-oxidant pathway to prevent apoptosis. Since radiotherapy efficacy depends on adequate DNA damage caused by free-radical generation, increased expression of bcl-2 may result in tumours becoming less responsive to radiation. Mutation of the p53 gene, however, is a rare event in cervical cancer. Since bcl-2 is negatively regulated by p53, it could be presumed that the p53 detected in the tumour cells may be non-functional or inactive possibly because of interaction with proteins such as E6 or mdm-2.
Division of Laboratory Medicine, Regional Cancer Centre, Thiruvananthapuram, Kerala State, India. rcctvm@md2.vsnl.net.in
M R
MR
Pillai
P G
PG
Jayaprakash
M K
MK
Nair
D002467:Cell Nucleus / Q000737:chemistry; D003593:Cytoplasm / Q000737:chemistry; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D018365:Neoplasm, Residual; D016017:Odds Ratio; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D002583:Uterine Cervical Neoplasms / Q000737:chemistry / Q000473:pathology / Q000532:radiotherapy*
D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53