Alterations Found in p16/Rb/Cyclin D1 Pathway in the Dysplastic and Malignant Cervical Epithelium

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Abstract
Cervical cancer is the one of the most common cancers affecting the south Indian women. The objective of the present study was to analyze the pl6/Rb/cyclin D1 pathway in the normal (n=30), dysplastic (n=56), and malignant cervical epithelium (n=142) using immunohistochemistry. The positive immunoreactivity for p16 was as follows: CIN I--1/12 (8.3%), CIN II--2/8 (25%), CIN III--31/36 (86.1%), and in invasive tumors-121/142 (85.1%); for cyclin D1 it was CIN I--4/12 (66.6%), CIN II--5/8 (62.5%), CIN III--0%, and invasive tumors--5/142 (3.5%); and for pRb it was CIN I--9/12 (75%), CIN II--5/8(62.5%), CIN III--1/36 (97.2%), and in invasive tumors--41/142 (28.8%). Expression of cyclin D1 and p16 in the CINs were mutually exclusive and the correlation between the two biomarkers was found to be statistically significant (p = 0.0009). There was downregulation of pRb in invasive cancers, with only 32% (39/121) of the p16-positive tumors being positive for pRb (p = 0.032). Analysis of the pattern of expression of these biomolecules showed increased p16-positive phenotypes and decreased cyclin D1- and pRB-positive phenotype among the invasive tumors compared to low-grade CIN lesions.

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