Immunohistochemical Study of p16INK4A, MIB-1 and CK17 in Pre-neoplastic and Neoplastic Epithelial Lesions of Cervix.

Abstract

Background: Cervical intraepithelial neoplasia (CIN) II and CIN III have a high progression rate to invasive squamous cell carcinoma (SCC). Histopathological assessment is known to have intra and inter-observer diagnostic discrepancies even among two panels of pathologist. Subsequently, to improve on the accuracy of histopathological examination, various IHC biomarkers have been evaluated in the biopsy of cervix.

Aim: The present study was undertaken to evaluate the immunoexpression and interrelationship of p16INK4A, MIB-1 and CK17 in histopathologically diagnosed cases of CIN and invasive cervical carcinoma (ICC) which could aid in differentiating CIN and ICC from benign cervical lesions.

Materials and methods: This study included 120 cases of cervical lesions; out of which 20 cases were each of negative for malignancy/dysplasia (NED), CIN I and CIN III, 10 cases of CIN II and 50 cases of ICC. A technique of manual tissue microarray was employed for the study of immunohistochemical markers such as p16INK4A, CK17 and MIB-1 in all cases. Results were subjected to statistical analysis.

Results: The difference in p16 immunoexpression between NED (0/20, 0%) and CIN+ICC (97/100, 97%) cases was statistically highly significant. (p<0.01) The sensitivity, specificity, positive and negative predictive value and diagnostic accuracy of p16 immunoexpression in comparison to histopathological diagnosis was 97%, 100%, 100%, 86.96% and 97.5% respectively. The overall agreement of p16 staining with histopathological diagnosis was 97.5% (?=0.9151 i.e. very good) The difference in MIB-1 immunoexpression between CIN-I (6/20, 30%) and CIN II+III (30/30, 100%), CIN (36/50,72%) and ICC (50/50, 100%) cases was statistically highly significant. (p<0.01) The difference in MIB-1 immunoexpression between NED (0/20, 0%) and CIN+IC (86/100, 86%) cases was statistically highly significant. (p<0.01) The sensitivity, specificity, positive and negative predictive value and diagnostic accuracy of MIB-1 immunoexpression in comparison to histopathological diagnosis was 86%, 100%, 100%, 58.82% and 88.33% respectively. The overall agreement of MIB-1 staining with H&E diagnosis was 88.33%. (?=0.6719 i.e. good) The difference in CK17 immunoexpression between CIN-I (11/20, 55%) and CIN-II+III (26/30, 86.67%) cases was statistically significant. (p=0.030) The difference in CK17 immunoexpression between CIN (37/50, 74%) and ICC (46/50, 92%) cases was statistically significant. (p=0.033) The difference in CK17 immunoexpression between NED (0/20, 0%) and CIN+ICC (83/100, 83%) cases was statistically highly significant. (p<0.01) The sensitivity, specificity, positive and negative predictive value and diagnostic accuracy of CK 17 immunoexpression in comparison to histopathological diagnosis was 82%, 100%, 100%, 52.63% and 85% respectively. The overall agreement of CK 17 staining with histopathological diagnosis was 85% (?=0.6029 i.e. moderate) The agreement between p16 and MIB-1 immunostaining was 89.16%. (?= 0.7 i.e., good) The agreement between CK17 and MIB-1 immunostaining was 86.6%. (?= 0.683 i.e., good) The agreement between p16 and CK17 immunostaining was 84.16%. (?= 0.5908 i.e., moderate) Conclusion: The findings of the present study indicate that the IHC report of p16, MIB-1 and CK-17 in CIN and ICC cases if included in each histopathology report could aid in accurate diagnosis which could facilitate in better patient management.