Cyclooxygenase-2 expression in intraepithelial neoplasia and squamous cell carcinoma of the uterine cervix and its clinicopathological relations

ABSTRACT

Cyclooxygenase [COX]-2 is involved in the genesis of many tumors; multiple lines of evidence suggested that selective inhibitors of [COX-2] are a novel class of therapeutic and chemopreventive agents for epithelial malignancies. The aim of this study was to investigate the expression of COX-2 in cervical intraepithelial neoplasia [CIN] and squamous cell carcinoma [SCC] of the uterine cervix and its association with Clinicopathological parameters. Twenty one patients with stage I-IV SCC of the cervix, another 21 patients with CIN I-III and 6 patients with histologically normal cervices were included in this study. Patients in the SCC group were treated with radical hysterectomy plus pelvic and para-aortic lymphadenectomy or anterior pelvic exentration. Immunohistochemical study was performed on paraffin embedded tissue sections with COX-2 antibody. Expression of COX-2 was demonstrated in SCC and CIN groups, while it was undetectable in normal cervices. In this study, the prevalence of positive COX-2 expression in SCC group was significantly higher than its prevalence in CIN group [66.7% Vs. 38.1%, p=0.03]. Significantly higher expression of COX-2 was reported in patients with FIGO stage II-IV compared to patients with FIGO stage I [83.3% Vs. 44.4%, p=0.05]. Additionally, patients with parametrial invasion had significantly higher COX-2 expression than patients without [90.0% Vs. 45.5%, p=0.04]. Furthermore, there was significant relationship with respect to COX-2 expression and lymph node involvement [p=0.04]. Regarding the relation between COX-2 expression in both tumor cells and tumor associated tissue eosinophils [TATE], statistically significant inverse relation was reported [p=0.03]. However, the statistical evaluation of COX-2 expression according to age, tumor size, histological type, lymphovascular space invasion [LVSI] and grade of differentiation demonstrated no significant relationship. Our results suggested that, COX-2 expression may have a role in the development and progression of CIN. COX-2 expression is related to most of clinicopathologic and prognostic variables of cervical carcinoma and may be incorporated into the criteria for determination of tumor aggressiveness. The role of COX-2 expression in cancer development and progression makes it a good target for therapy and selective COX-2 inhibitors may be a promising strategy not only for chemoprevention but also for therapeutic approaches in SCC of the uterine cervix