COX-2 Expression in Primary Tumor and Lymph Node Metastases as a Prognostic Marker in Prostate Cancer

Background: Prostate cancer remains one of the most common malignancies in men, and prognosis remains particularly challenging in patients with lymph node metastases. Cyclooxygenase-2 (COX-2), an inducible enzyme involved in inflammation and tumor progression, has been proposed as a potential prognostic biomarker and therapeutic target. While COX-2 overexpression in primary prostate tumors has been reported, its expression in lymph node metastases has not been thoroughly investigated. Methods: This study included 77 treatment-naïve patients with prostate cancer and histologically confirmed lymph node metastases who underwent radical prostatectomy with extended lymphadenectomy. COX-2 expression was assessed using immunohistochemistry in paired samples from primary tumors and corresponding lymph node metastases. Statistical comparisons were conducted using the Mann–Whitney U test and survival analyses were performed using Kaplan–Meier curves with the log-rank test. Results: COX-2 expression was detected in both primary tumors and lymph node metastases, with no significant difference in staining intensity between the two sites. High COX-2 expression in primary tumors was significantly associated with a higher percentage of involved lymph nodes (30.0% vs. 11.8%, p = 0.026), elevated postoperative PSA levels (1.98 vs. 0.10 ng/ml, p = 0.007), and reduced surgical radicality (11.1% vs. 63.2%, p = 0.008). Moreover, elevated COX-2 expression in both primary and metastatic tissues correlated with worse five-year overall survival (41.7% vs. 92.8%, p = 0.033; and 40.0% vs. 95.6%, p < 0.001, respectively). Conclusions: High COX-2 expression is associated with adverse clinicopathological features and poorer survival in lymph node–positive prostate cancer. These findings suggest that COX-2 is not only a marker of tumor aggressiveness, but may also contribute to disease progression through facilitating lymphangiogenesis. Given its strong association with adverse outcomes, COX-2 may serve as a clinically relevant prognostic biomarker in lymph node-positive PC. Further prospective studies are needed to validate its prognostic utility and assess its potential as a therapeutic target.