Co-expression of p53 and Bcl-2 proteins in human papillomavirus-induced premalignant lesions of the uterine cervix: correlation with progression to malignancy.

OBJECTIVE(S): To analyze aberrant expression of the apoptotic protein p53 and the anti-apoptotic protein Bcl-2 in premalignant lesions of the uterine cervix induced by human papillomavirus (HPV) infection and its significance for early diagnosis of cervical cancer.

MATERIALS AND METHODS: Cytological adequate smears (n = 382) from various grades of squamous intraepithelial lesions (SILs; n = 142), 'atypical squamous cells of unknown significance' (ASCUS; n = 128) and normal tissue (n = 112) were investigated immunocytochemically for aberrant expression of p53 and Bcl-2 proteins using the streptavidin-biotin-peroxidase method; HPV status was analyzed in cervical smears using general and type-specific primers.

RESULTS: HPV-DNA of any type was detected in 25.7% (98/382) of cases. HPV16 was seen in 58.2% (57/98), HPV18 in 20.4% (20/98) and other HPV types in 21.4% (21/98). Abnormal nuclear expression of p53 protein and cytoplasmic expression of Bcl-2 protein were noted in cervical dysplasia and an association with the presence of HPV16/HPV18 was noted. The intensity of immunoreactivity for p53 and Bcl-2 proteins varied between different cytological grades of cervical smears. Follow-up data revealed that cases with high-risk HPV and co-induced expression of apoptosis-regulatory proteins presented a trend to progressive disease.

CONCLUSIONS: The detection of both p53 and Bcl-2 proteins in cervical smears can be used as independent diagnostic marker for early-stage HPV-associated cervical cancer.