Differential expression of cyclin-dependent kinase inhibitors and apoptosis-related proteins in endocervical lesions

The development of neoplasia is associated with abnormalities of cell cycle control and apoptosis. In this study, a panel of cyclin-dependent kinase inhibitors (CDKIs) and apoptosis-related proteins (p16, p21, p53, Bcl2 and hsp27) was analysed by immunohistochemistry in 91 glandular cervical lesions. A significant increase in p21 and p53 expression occurred from normal cervix (n = 11) through endometriosis/tubo-endometrioid metaplasia (TEM) (n = 19) and cervical glandular intraepithelial neoplasia (CGIN)/adenocarcinoma in situ (AIS) (n = 33) to invasive adenocarcinoma (n = 28). p16 showed diffuse strong expression in CGIN/AIS and invasive adenocarcinoma compared with focal expression in some TEM/endometriosis lesions and no expression in normal cervix. Bcl2 was highly expressed in TEM/endometriosis compared with CGIN/AIS and adenocarcinoma. p16 immunostaining discriminated accurately between neoplastic and non-neoplastic cervical lesions, provided that diffuse strong positivity was present. Similarly, diffuse expression of Bcl2 distinguished endometriosis/TEM from CGIN/AIS. These data demonstrate that analysis of CDKIs and apoptosis-related proteins provides useful information in the diagnostic assessment of glandular lesions of the cervix.