Evaluation of Her- 2 neu over expression in morphological variants of cervical carcinomas using immunohistoichemistry: A study of 25 cases.

Introduction: Carcinoma of uterine cervix is the second most prevalent cancer among women worldwide and remains a major gynecological malignancy in developing countries. HER-2/neu,a pro-oncogene is a cell membrane surface bound tyrosine kinase receptor  and is involved in signal transduction pathway leading to cell growth and differentiation. Aim: The present study is conducted to evaluate the over-expression of HER-2/neu in carcinoma cervix, its pattern of membranous staining and correlation with histological type, grade of tumor and stage of disease wherever available. Methods: A part retrospective and part prospective study was done on a total of 25 cervical biopsies and hysterectomies specimen. Tissue blocks with extensive necrosis or hemorrhage were excluded from the study and  immunohistochemistry  for HER-2/neu was done. The percentage of cells showing the membranous positivity for HER2/neu, extent of its positivity in the cervical epithelium in different lesions of the cervix and membranous intensity of HER2/neu positive cells was noted. The HER2/neu expression was then correlated with morphological diagnosis, grade of lesion, invasion and lymph node metastasis in hysterectomies. Results: 18 cases were reported to be SCC (72%) , while Adenocarcinoma (12%)  and Adenosquamous (16%) carcinoma constituted small subgroups of 3 and 4 cases, respectively,  13(52%)  cases of carcinoma cervix were found to be positive for HER 2/neu while 12/25 cases(48%) were negative. 11 cases of SCC were positive for HER2/neu, 2/4 adenosquamous carcinoma cases  were positive. No adenocarcinoma cases were found to be  positive  for HER2/neu. 12 carcinoma cervix cases show 20% (6%). Of the 19 of carcinoma cervix with known staging,  (9)  were of stage 1, 1/9 cases of stage I   showed HER2/neu positivity (2+),  4/6 of stage II were moderately positive (2+) for the marker 2/ 2 of  stage IV cases showed 2+ and 3+ positivity. The present study showed SCC to be the most common carcinoma with 52% of carcinoma cervix cases expressed positivity for HER-2/neu. Maximum number of carcinoma cases showed 2+ HER-2/neu  intensity. HER-2/neu positivity was found to be highest in SCC, followed by adenosquamous and adenocarcinoma. Her 2/neu was found to be over expressed in higher stage with high percentage positivity. Conclusion: The high incidence of HER-2/neu  amplification  in  cervical  cancer suggests the role of this gene in tumorigenesis and this study emphasize HER-2/neu overexpression in cervical carcinoma.