Proliferative Activity of Benign and Neoplastic Endocervical Epithelium and Correlation with HPV DNA Detection

Abstract

Recent studies have indicated that the use of the MIB-1 immunostaining may be useful in distinguishing endocervical neoplasia from benign nonneoplastic lesions. We sought to investigate this finding further with a specific emphasis on the common benign processes that may result in a nonspecific increase of MIB-1 staining. In this study we quantified the MIB-1 immunostaining in the mucinous endocervical epithelium (n=45) and in tubal metaplasia (n=28) during the proliferative and secretory phases (hormonal influence), in the mucinous endocervical epithelium in cases of cervicitis (inflammation) (n=10), in cases with a history of a recent biopsy (regeneration) (n=15), endocervical polyps (benign growth) (n=8), in the endocervical glands adjacent to a squamous intraepithelial lesion (human papilloma virus [HPV] infection) (n=63), and in in situ and invasive cervical adenocarcinomas (n=30). All cases with increased MIB-1 staining were subsequently tested for the presence of HPV DNA. The range of MIB-1 staining in the benign endocervical epithelium was from 0% to 48% and in the neoplastic epithelium from 25% to 84%. MIB-1 staining below 10% always reflected a benign process and MIB-1 staining higher than 50% was always associated with a neoplasia. Rare benign cases (tubal metaplasia during the proliferative phase, glands adjacent to squamous intraepithelial lesions, and cases with a history of a recent biopsy) had increased MIB-1 index, which overlapped with the neoplastic cases. In conclusion, MIB-1 is a useful marker of endocervical neoplasia, although in rare cases an overlap between benign and neoplastic cases may exist.

Immunohistochemical Differences Between Mucinous and Microglandular Adenocarcinomas of the Endometrium and Benign Endocervical Epithelium

“…Differentiating mucinous endometrial tumor from mucinous endocervical adenocarcinoma is less problematic than differentiating mucinous endometrial adenocarcinoma from benign endocervical epithelium. In contrast to mucinous endometrial tumors, endocervical adenocarcinomas show brisk mitotic activity with an average Ki-67 staining score of 50% (19), as well as low scores of vimentin, ER, and PR positivity (17,18).…”

“…Vimentin is expressed in virtually all mesenchymal cells and few epithelia, which include benign and neoplastic endometrial glands. Ki-67 is a marker of cellular proliferation that shows increased staining in benign, hyperplastic, and malignant endometrial epithelium, but not in benign endocervical glands (19). p16, a cell cycle regulatory protein, has been shown to be overexpressed in endometrial adenocarcinomas and benign tubal metaplasia of the cervix, but not in benign mucinous endocervical glands (20).…”

Diverse facets of cervical adenocarcinoma: comprehensive review of clinicopathologic features and diagnostic criteria

“…Of note, TEM may show mitotic activity during the proliferative phase of the cycle, however, no nuclear atypia is seen in such glands. 8 Cervical endometriosis is easily identified when both endometrial glands and endometrial stroma composed of small, plump, blue cells are present in the same focus. The diagnosis is more difficult when there is only a thin rim of stromal cells and when the glands show mitotic activity in the proliferative phase.…”

Immunohistochemical and Functional Biomarkers of Value in Female Genital Tract Lesions

“…Similarly in the endocervix, MIB1 helps to distinguish endocervical AIS and benign mimics such as tuboendometrial metaplasia, endometriosis and microglandular hyperplasia (MGH) (88,160,161,169,170). Benign mimics usually exhibit a low MIB1 proliferation index of G10% whereas in most cases of AIS the proliferation index is in excess of 30%, usually much greater.…”