Abstract

Background/aim: It is generally assumed that similar pathways are involved in human papillomavirus (HPV) induced pathogenesis of cervical squamous intraepithelial lesions (SILs) and cancers and a subset of conjunctival intraepithelial neoplasm (CIN)—that the malignancies or pre-cancerous lesions arise through HPV oncoproteins E6 and E7, which disrupt the pathways of p53 and the product of the retinoblastoma (Rb) gene and, in turn, increase the protein product of gene p16^INK4 through the mechanism of positive feedback. Several cell cycle molecules are detected to test this hypothesis.

Methods: Nine cases of CIN and eight non-CIN cases were analysed for the expression of Ki-67, pRb, p53, and p16^INK4 via immunohistochemistry. Nine cases of cervical high grade squamous intraepithelial lesion (HSIL), and 10 cases of cervical low grade squamous intraepithelial lesion (LSIL) were included for stain control of p16^INK4a, and comparison of p16^INK4a expression to CIN cases. A nested polymerase chain reaction and a genechip HPV typing were used to detect HPV infection and types in the CIN and non-CIN samples

Results: HPV positivity was demonstrated in all of the CIN lesions but in none of the non-CIN lesions. The Ki-67 proliferative index (Ki-67 PI) was statistically higher in the CIN group than the non-CIN group; however, there were no differences of expression of pRb and p53 between the two groups and no expression of p16^INK4 in all cases. All nine cases of HSIL, and seven out of 10 cases of LSIL used for stain control were immunoreactive for p16^INK4a. There were statistically significant differences in overexpression of p16^INK4a between the CINs and SILs

Conclusions: The Ki-67 proliferative index may be a sensitive marker for CIN lesions and these results, with significant differences in overexpression of p16^INK4a between CINs and SILs, may provide new evidence that HPV related mucosal dysplasia in different anatomical locations may lead to dissimilar molecular pathways.