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

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. © 2003 Elsevier Inc. All
rights reserved.