Overexpression of cyclins A and B as markers of neoplastic glandular lesions of the cervix

Abstract

Introduction: Cyclins are a family of regulatory proteins that play a pivotal role in controlling the cell cycle. While there is evidence of their altered expression in cervical squamous lesions, their precise role in glandular neoplasia is yet to be elucidated.

Objectives: To investigate the role of cyclins as markers of early cervical glandular neoplasia by comparing their expression in lesions of different histological type.

Methods: Through a cross-sectional analytical study, paraffin wax sections of normal cervix (n = 11), endometriosis/tubo-endometrioid metaplasia (TEM) (n = 19), cervical glandular intraepithelial neoplasia (CGIN) (n = 33), and invasive adenocarcinoma (n = 28) were studied using monoclonal antibodies for cyclins A, B, D, and E with heat pretreatment for antigen unmasking. A quantitative assessment was employed for the analysis of percentage expression of each marker. Statistical analysis of data was performed using SPSS.

Results: A progressive significant increase in cyclin A expression occurred from normal cervix (median: 0, IQ: 0-0), through endometriosis/TEM (median: 1, IQ: 0-15) and CGIN (median: 15, IQ: 0-30) to invasive adenocarcinoma (median: 40, IQ: 21.25-60). Cyclin B exhibited a similar pattern (median: 0, IQ: 0-0, median: 0, IQ: 0-0.5, median: 8, IQ: 0.75-15, and median: 30, IQ: 15-45, respectively). Statistically higher expression of cyclin B was found in CGIN than in TEM/endometriosis (P < 0.001). Invasive adenocarcinomas expressed higher levels of cyclins A and B than CGIN (P < 0.001). There was significantly greater cyclin E expression in TEM/endometriosis than in normal cervix (P = 0.03) with a nonsignificant further increase in CGIN and invasive adenocarcinoma. The expression of cyclin D was not significantly different among all groups.

Conclusions: Our data indicate that up-regulation of cyclin A and B expression occurs in neoplastic lesions of the cervix. Cyclin B expression was significantly more widespread in CGIN lesions than in TEM/endometriosis indicating that further assessment of the value of this marker in the diagnosis of cervical glandular neoplasia is warranted.