Evaluation of p16 INK4a and pRb expression in cervical squamous and glandular neoplasia

Abstract

p16 INK4a is known to play a critical role as a negative regulator of cell cycle progression and differentiation by controlling the activity of the tumor-suppressor protein pRb. The present study evaluated the expression of p16 INK4a and pRb in cervical squamous and glandular neoplasia. Immunohistochemical staining was performed for p16 INK4a and pRb in formalin-fixed, paraffin-embedded tissue sections of the uterine cervix using an indirect immunoperoxidase method. p16 INK4a staining was detected in 7 of 108 sections (6.5%) of normal squamous mucosa, in scattered ciliated columnar cells in 33 of 88 sections (37.5%) of normal endocervical glands, in 9 of 30 sections (30%) with Nabothian cysts, and in 4 of 4 areas (100%) of tubal metaplasia. In contrast, strong p16 INK4a staining was found in 13 of 18 cases (72.2%) of cervical intraepithelial neoplasia (CIN) I and in all cases of CIN II/III (n = 46), squamous cell carcinoma (n = 18), endocervical glandular dysplasia (n = 10), adenocarcinoma in situ (n = 23), and invasive adenocarcinoma (n = 12). pRb expression was detected in each diagnostic category; however, the proportion of pRb-positive cells was relatively decreased in high-grade premalignant and malignant lesions of the squamous and endocervical mucosa and showed a generally inverse correlation with the expression of p16 INK4a at the tissue level. These findings confirm a correlation between the expression of p16 INK4a and pRb in cervical neoplasias and indicate that p16 INK4a is a specific marker for premalignant and malignant lesions of the squamous and endocervical mucosa.