Prognostic role of the ratio between cyclooxygenase-2 in tumor and stroma compartments in cervical cancer

Purpose: The aim of this study was to analyze the clinical role of cyclooxygenase (COX)-2 in a large series of 175 cervical cancer patients. Experimental Design: Immunohistochemistry was performed on paraffin-embedded sections by using rabbit an-tiserum against COX-2. The tumor:stroma (T/S) ratio of COX-2 expression was used to define the overall COX-2 content in the tumor. Results: The T/S COX-2 ratio values ranged from 0.03 to 48.2 (mean +/- SE, 3.7 +/- 0.5). A total of 95 of 175 patients (54.3%) were scored as having a high (>1) T/S COX-2 ratio. In locally advanced cervical cancer patients who underwent neoadjuvant treatment, the percentage of cases showing a high T/S COX-2 ratio was greater in patients who did not respond to treatment (26 of 29 patients, 89.7%) than in patients with a partial (32 of 50 patients, 64.0%) or complete (19 of 44 patients, 43.2%) response (P = 0.0003). When logistic regression was applied, International Federation of Gynecologists and Obstetricians (FIGO) stage (X-2 11.3; P = 0.0008) and T/S COX-2 ratio (X-2 = 5.3; P 0.021) retained an independent role in predicting a poor chance of response. Cases with a high T/S COX-2 ratio had a shorter overall survival (OS) [2-year OS, 61%(95% confidence interval 750-83)] than cases with a low T/S COX-2 ratio (2-year OS, 90%; 95% confidence interval, 81-99; P = 0.0001). In multivariate analysis, the status of T/S COX-2 IDV ratio, together with advanced stage, retained an independent negative prognostic role for OS. Conclusions: The assessment of COX-2 status in both tumor and stroma compartment could provide valuable information to identify cervical cancer patients endowed with a very poor chance of response to neoadjuvant treatment and unfavorable prognosis.