Evaluation of Telomerase (hTert), Ki67 and p16ink4a expressions in low and high-grade cervical intraepithelial lesions.

Ana Paula Szezepaniak Goulart,Vinicius Duval Da-Silva,Manoel Afonso Guimarães Gonçalves

doi:10.1590/0100-69912017002005

Abstract

to study the association between the histological grading of cervical intraepithelial neoplasia (CIN I, CIN II and CIN III) and the immunohistochemical expression for p16ink4a, hTert and Ki67, as well as to evaluate the relationship of these markers with the risk of recurrence after surgical treatment. we studied a historical cohort of 94 women with intraepithelial lesions CIN I (low grade), CIN II and CIN III (high grades) submitted to conization or electrosurgical excision of the transformation zone. We evaluated all surgical specimens for immunohistochemical expression of p16ink4a, hTert and Ki67. the mean age was 38.2 years; p16ink4a was absent in most CIN I cases. In patients with CIN II or I/II (association of low and high-grade lesions), we observed p16ink4a ≤10%. In patients with CIN III, we found a higher expression frequency of p16ink4a >50%. In CIN I, the majority had Ki67≤10% and low frequency of Ki67>50%. In the CIN III category, there were fewer patients with Ki67≤10%, and Ki67 was absent in most patients of CIN II and III groups. There was no association between hTert expression and histologic grade. There were no statistically significant differences between the expression of the markers in patients with and without recurrence. there was a statistically significant association of p16ink4a and Ki67 with histological grade. The markers' expression, as for disease recurrence, was not statistically significant in the period evaluated.

Highlights

Cervical cancer is the third most common malignant neoplasm among women (90% of cases in developing countries), and in Brazil it accounts for 9.3% of gynecological malignancies
The malignant neoplasm of the cervix is preceded by a long phase of precursor, usually asymptomatic, lesion, characterized by cervical intraepithelial neoplasia (CIN), which may persist for 10 to 20 years
The use of molecular markers has helped the pathologists in the definition of doubtful cases and in the identification of women at high risk for disease recurrence after treatment of cervical intraepithelial neoplasias5. p16ink4a, a tumor suppressor protein, is overexpressed in cases of dysplasia, presenting a high sensitivity as it correlates with the dysplasia severity

Summary

Introduction

Cervical cancer is the third most common malignant neoplasm among women (90% of cases in developing countries), and in Brazil it accounts for 9.3% of gynecological malignancies. Infection is more common in young patients; sexual behavior, age, smoking, parity and use of contraceptives are risk factors for this neoplasia[1]. The use of molecular markers has helped the pathologists in the definition of doubtful cases and in the identification of women at high risk for disease recurrence after treatment of cervical intraepithelial neoplasias. Current studies indicate that p16ink4a is a useful biomarker for high-risk lesions and for progression prediction in low-risk ones. These studies show a significant association between the degree of cervical lesion and the distribution and intensity of p16ink4a expression[5,6]

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Results