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

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Basal cell tetrasomy in low grade squamous intraepithelial lesions of the cervix is associated with infection by high and intermediate risk but not low risk human papillomaviruses (HPVs). It is known that the viral E6 and E7 proteins interact with p53 and p21, respectively, altering cell cycle control and leading to chromosomal instability. In this study, p53 and p21 expression was analyzed in disomic and tetrasomic low grade squamous intraepithelial lesions infected with a wide range of HPV types. HPV identification and typing was performed using both in situ hybridization and the polymerase chain reaction followed by dot blot hybridization with specific HPV probes. Interphase cytogenetic analysis using centromeric chromosomal probes also performed was to identify numeric chromosomal abnormalities. The expression of p53 and p21 was studied by immunohistochemistry using monoclonal antibodies specific for these proteins. 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 analyzed according to the distribution of expression by using 3 groups, focal, regional, and diffuse (Pearson coefficient, r = 0.47, P < 0.001). In the lesions infected with intermediate/high risk HPVs, expression of p53 was significantly decreased or completely absent in tetrasomic areas, whereas expression of p21 was similar in both disomic and tetrasomic regions. The authors' data suggest that low, intermediate, and high risk HPVs have different effects on p53 and p21 protein expression, and that the induction of numeric chromosomal abnormalities by intermediate/high risk HPVs may be related to altered expression of p53.