Differential expression of p53 and p21 in low grade cervical squamous intraepithelial lesions infected with low, intermediate, and high risk human papillomaviruses

BACKGROUND. Basal cell tetrasomy in low grade squamous intraepithelial lesi ons of the cervix is associated with infection by high and intermediate ris k but not low risk human papillomaviruses (HPVs). It is known that the vira l E6 and E7 proteins interact with p53 and p21, respectively, altering cell cycle control and leading to chromosomal instability. In this study, p53 a nd p21 expression was analyzed in disomic and tetrasomic low grade squamous intraepithelial lesions infected with a wide range of HPV types. METHODS. HPV identification and typing was performed using both in situ hyb ridization and the polymerase chain reaction followed by dot blot hybridiza tion with. specific HPV probes. Interphase cytogenetic analysis using centr omeric chromosomal probes also performed was to identify numeric chromosoma l abnormalities. The expression of p53 and p21 was studied by immunohistoch emistry using monoclonal antibodies specific for these proteins. RESULTS. Increased expression of p53 and p21 was more widespread in lesions infected with low risk than with intermediate/high risk HPV types (p53, P < 0.001; p21, P < 0.01). p53 status correlated with p21 expression when ana lyzed according to the distribution of expression by using 3 groups, focal, regional, and diffuse (Pearson coefficient, r = 0,47, P < 0.001). In the l esions infected with intermediate/high risk HPVs, expression of p53 was sig nificantly decreased or completely absent in tetrasomic areas, whereas expr ession of p21 was similar in both disomic and tetrasomic regions. CONCLUSIONS. The authors' data suggest that low, intermediate, and high ris k HPVs have different effects on p53 and p21 protein expression, and that t he induction of numeric chromosomal abnormalities by intermediate/high risk HPVs may be related to altered expression of p53. (C) 2000 American Cancer Society.