The Use of Molecular Markers (p16, Ki-67 and E-Cadherin) in Uterine Cervical Biopsies

Abstract

Introduction: Cervical cancer is related to the Human Papillomavirus (HPV). The E7 viral DNA sequence in- duces the start of DNA synthesis of infected cell, releasing protein p16. The sequence E6 inhibits apoptosis, with pro- longed survival of cells heavily damaged and changed, with inhibition of p53 protein and increasing of protein Ki-67. In those injured cells, the molecules are reduced to join the cell membrane, the type E-cadherin. Aim: To study the expression of p16 protein in: normal epithelium cervical, cervical lesions, pre-invasive (CIN) persistent and no persistent lesions and invasive carcinoma of the cervix and to correlate with the expression of Ki-67 and E- cadherin. Patients and Methods: 54 uterine cervix biopsies were selected and submitted to immunohistochemical study, with bio- markers p16, Ki-67 and E-cadherin. Results: 1 CIN I (27.9%) and CIN II (47.9%) had lower expression of p16 than in CIN III (73.5%) and invasive carcinoma (72.7%) (p < 0.0005). For Ki-67, invasive carcinoma (57.8%), had a higher expression when compared to CIN I (35.6%), CIN II (51.9%) and CIN III (40.9%) (p = 0.005). E-cadherin expression in invasive carcinoma (46.2%) was lower than in CIN III (56.0%), CIN II (77.4%) and CIN I (82.2%) (p < 0.0005) and, normal epithelium had the greatest E-cadherin ex- pression (89.1%). In persistent and no persistent CIN there was no difference in the expression of the biomarkers, with p16 presenting p = 0.50, Ki-67, p = 0.91 and the E-cadherin a p = 0.43 value. Conclusions: The use of p16, Ki-67 and E-cadherin biomarkers in cervical biopsies with difficult diagnosis could help in the early diagnosis of malignant lesions and support adequate treatment, 2. There is no association between the diagnosis of the biopsy and the persistence of the cervical lesion and, 3. The used biomarkes don't differentiate between persistent CIN and no persistent lesions.