Cyclooxygenase-2 as a Prognostic Biomarker in Colorectal Cancer: Immunohistochemical Assessment and Correlation with Clinicopathological Parameters and Disease-free Survival in a Kashmiri Cohort

Abstract

Colorectal cancer (CRC) is a major global disease with an increasing incidence in South Asia, especially the Kashmir valley. Cyclooxygenase-2 (COX-2), an inducible enzyme that converts arachidonic acid to prostaglandins, promotes tumorigenesis via angiogenesis, apoptosis resistance, invasion, and immune evasion. Its predictive value in regionally different populations is not fully understood. The study aims to assess COX-2 immunohistochemistry (IHC) expression in CRC patients from Kashmir and investigate its correlation with clinicopathological characteristics and disease-free survival (DFS). Forty-seven histologically confirmed CRC cases were enrolled from a tertiary care centre in Kashmir from January 2024 to December 2025. COX-2 IHC was performed on FFPE sections and scored using the Remmele immunoreactive score (IRS). Sample size was justified using a two-proportion power analysis based on published event rates. Associations with clinicopathological variables were assessed by Fisher’s exact test; DFS was evaluated by Kaplan–Meier methodology with log-rank testing. COX-2 positivity (moderate + strong) was 76.6%. Strong expression (score 2; IRS ≥ 9) was present in 40.4% of cases and was significantly associated with early recurrence ( P = 0.0002). Of 19 strongly positive patients, 68.4% recurred within 24 months versus 14.3% in the moderate/negative group. The odds of recurrence were 13-fold higher with strong COX-2 expression (odds ratio = 13.0; 95% confidence interval: 3.1–54.5). Kaplan–Meier analysis confirmed markedly inferior DFS in the strong-expression cohort. COX-2 overexpression was associated with early recurrence and shorter DFS. These findings suggest that COX-2 expression may have prognostic value, although larger multicentre studies are required before routine clinical implementation.