Co-overexpression of p53 and bcl-2 proteins in HPV-induced squamous cell carcinoma of the uterine cervix☆

Abstract

Objective The aim of this study was to analyze aberrant expression of both apoptotic protein p53 and antiapoptotic protein bcl-2 in squamous cell carcinoma (SCC) of the uterine cervix with HPV infection and its significance as a marker for progression of cervical lesions. Methods One hundred and five cervical lesions and 20 normal (age matched) cervical epithelium from patients with complaints other than cervical lesions were investigated immunocytochemically for aberrant expression of p53 and bcl-2 using the streptavidin-biotin-peroxidase method with respective monoclonal antibodies. HPV status was also anlayzed using type-specific primers for HPV 16/18 and HPV 6/11 by polymerase chain reaction (PCR). The statistical correlation analysis was carried out using Spearman's correlation test and univariate analysis by the SPSS system. Results An abnormal nuclear expression of tumor-suppressor protein p53 and cytoplasmic expression of bcl-2 were observed using immunocytochemistry in biopsies of cervical lesions but not in normal subjects. The intensity of immunoreactivity for both p53 and bcl-2 proteins varied between different histopathological grades of cervical lesions and the correlation analysis showed a highly significant positive correlation for their expression level with different stages from mild dysplasia to invasive cancer with r = 0.88842; P = 0.00001 and r = 0.86929; P = 0.00001, respectively. A highly significant positive correlation was also observed between the expression of both p53 and bcl-2 proteins and HPV infection. The current study indicates a very good significant direct correlation ( r = 0.83925; P = 0.00001) between p53 expression and bcl-2 expression in the study population, suggesting the co-overexpression of these proteins in HPV-associated cervical cancer. Conclusion From the observations it is suggested that the immunodetection of both p53 and bcl-2 proteins in squamous cell carcinoma of the uterine cervix can be used as an independent diagnostic marker for cervical cancer associated with HPV infection. The highly significant association of these proteins with HPV infection suggests that the high-risk HPV infection may be responsible for the co-overexpression of p53 and bcl-2 in cervical cancer even though both of them are antagonistic in their function. This study thus helps to understand the molecular mechanism underlying cervical carcinogenesis and which in turn may improve the therapeutic approach.