Immunohistochemical Study of Cyclin D1 and HER2/neu in Pre-neoplastic and Neoplastic Epithelial Lesions of Cervix.

Abstract

Background: Among cancers affecting women worldwide, cervical cancer is positioned at the fourth rank.

Aim: The present study was undertaken to evaluate the immunoexpression and interrelationship of cyclin D1 (CD1) and HER2/neu in histopathologically diagnosed cases of cervical intraepithelial neoplasia (CIN) and invasive cervical carcinoma (ICC) and its association with other clinicopathological parameters.

Materials and methods: This study included 120 cases of cervical lesions; out of which 10 cases were of negative for malignancy/dysplasia (NED), 15 cases of CIN I, 9 cases of CIN II and 21 cases of CIN III and 65 cases of invasive cervical carcinoma (ICC). A technique of manual tissue array was employed to study the expression pattern of CD1 and HER2/neu in all the cases. Results were subjected to statistical analysis.

Results: CD1 immunoexpression was statistically significantly higher in normal + LSIL (low grade squamous intraepithelial lesion) (CIN I) cases than HSIL (high grade squamous intraepithelial lesion) (CIN II+III) + ICC. As the severity of the cervical lesions increased, CD1 immunoexpression statistically significantly shifted from nucleus to cytoplasm. Statistically significant inverse relationship was noted between CD1 expression and grade of ICC cases. CD1 IHC marker showed 63.64% sensitivity, 0% specificity, 87.5% PPV and 0% NPV. The overall agreement of CD1 staining with H&E diagnosis was 58.33% (κ=0.1538 i.e. poor). HER2/neu immunoexpression increased statistically significantly with increasing severity of lesion from CIN-I to CIN-III to ICC. None of the NED cases in present study showed HER2/neu positivity. With increasing stage and grade of ICC, the percentage of cases expressing HER2/neu statistically significantly increased. Her2/neu IHC marker showed 56.63% sensitivity, 100% specificity, 100% PPV and 17.24% NPV. The overall agreement of HER2/ neu staining with H&E diagnosis was 60% (κ=0.1771 i.e. poor). The agreement between HER2/neu and CD1 immunostaining was 40%.

Conclusion: Cyclin D1 and HER2/neu IHC marker panel could be used as prognostic markers and could be routinely incorporated into the surgical pathology report which could aid in understanding the biology of the tumor and better patient management. ICC expressing CD1 and HER2/neu could benefit from specific targeted therapy.