The Immunohistochemical Assessment of HPV Related Adenocarcinoma: Pathologic and Clinical Prognostic Significance

Abstract

Although several epidemiologic studies have confirmed the association between high-risk human papillomavirus (hr-HPV) and adenocarcinoma of the cervix, there are few papers focusing on the molecular immunophenotype of the HPV related cervical adenocarcinoma and its precursor lesions. The present study is aimed to assess the immunohistochemical expression of p16, p53, cyclin D1, EGFR, and COX-2 in benign and malignant lesions of cervical glandular components, and consequently the identification of the relationship between these markers and the HPV L1 capsid protein. We investigated 7 cases of endocervical adenocarcinoma in situ (AIS), 8 cases of adenosquamous carcinoma, 15 cases of invasive adenocarcinoma of endocervical type, and 5 cases without malignant lesions (normal and/or benign endocervical epithelium). The tissue fragments underwent standard laboratory procedures for the histopathological and immunohistochemical exams. For each marker, the semi-quantitative assessment was performed using appropriate scoring systems. Our results showed that: (i) the combination of L1 capsid protein and p16 can predict the progression risk of precursor lesion of endocervical adenocarcinomas; (ii) p53 - COX2 - p16 co-assessment is useful as a panel of relevant biomarkers for L1 – p16 association; (iii) EGFR increases according to the progression in lesions severity; (iv) cyclin D1 is a reliable marker for the invasive capacity. Further studies are necessary to quantify the value of these markers, as prognostic factors in HPV related cervical adenocarcinoma. Keywords: HPV, cervical adenocarcinoma, adenosquamous carcinoma, immunohistochemistry, high-risk human papillomavirus (hr-HPV), precursor lesions, capsid protein, malignant lesions, marker, COX-2