COX-2 Expression in Paired Primary Tumors and Lymph Node Metastases: An Exploratory Clinicopathological Study

Background/Objectives: 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 investigated as a potential prognostic biomarker and therapeutic target, but its expression in lymph node metastases remains unclear. While COX-2 overexpression in primary prostate tumors has been reported, its expression in lymph node metastases has not been thoroughly investigated. Therefore, this study aimed to compare COX-2 expression in primary prostate tumors and corresponding lymph node metastases and to evaluate its association with clinicopathological characteristics and survival. 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. The association of COX-2 expression with the extent of lymph node involvement and survival suggests that COX-2 may have prognostic value in this setting. However, the present findings do not establish a causal role of COX-2 in disease progression or lymphangiogenesis. Further studies are warranted to validate the prognostic significance of COX-2 and to clarify its potential biological and therapeutic relevance in lymph node–positive prostate cancer.