Expression of cyclooxygenase-2 (COX-2) in non-neoplastic and neoplastic vulvar epithelial lesions

Abstract

Objective. Cyclooxygenase-2 (COX-2) overexpression has been associated with parameters of tumor aggressiveness and unfavourable clinical outcome in several solid tumors. We investigated by immunohistochemistry the expression of COX-2 in normal vulvar tissue, non-neoplastic vulvar epithelial lesions, vulvar intraepithelial neoplasia (VIN) and invasive vulvar cancer (IVC). Methods. The expression pattern of COX-2 was studied in normal vulvar tissue, in six cases of lichen sclerosus (LS), seven cases of squamous cell hyperplasia (SCH), 20 VIN, 2 Paget's disease and 36 IVC. The relationship between COX-2 expression and clinicopathologic parameters in IVC patients has been also addressed. Sections were incubated with normal rabbit serum for 15 min, then with rabbit polyclonal antiserum against human COX-2 (Cayman, Ann Arbor, MI, USA). The results were reported as mean ± standard error (SE) of COX-2 integrated density values (IDV). Results. Higher levels of tumor/stroma COX-2 IDV ratio were found in stages III–IV (mean ± SE = 3.5 ± 0.8) than stages I–II disease (mean ± SE = 1.4 ± 0.3) ( P value = 0.04). In the subgroup of stage I cases, tumor/stroma COX-2 IDV values were higher in cases with > 1 mm stromal invasion (T1b) than cases with ≤ 1 mm stromal invasion (T1a) (mean ± SE = 1.6 ± 0.3 vs. mean ± SE = 0.6 ± 0.1) ( P = 0.033). Moreover, we observed higher tumor/stroma COX-2 IDV in cases with metastatic lymph node involvement than cases without lymph node involvement (mean ± SE = 3.5 ± 0.8 vs. mean ± SE = 1.3±0.4) ( P = 0.037). Conclusion. This study suggests that COX-2 overexpression may contribute to vulvar tumorigenesis and progression. Moreover, the correlation of tumor/stroma COX-2 IDV ratio with tumor extension and metastatic lymph node involvement, which represent the major prognostic parameters in this neoplasia, implies that tumor/stroma COX-2 IDV ratio could have a prognostic role in vulvar cancer.