Abstract C043: Prognostic value of RAS mutations, HER2, and COX2 expression in colon cancer: A large Moroccan cohort study

Abstract Background. The pathogenesis of colorectal cancer (CRC) is characterized by a complex interplay of multiple molecular alterations that drive tumor development and progression. Among these alterations, RAS mutations and specific protein expressions are of particular interest. This exploratory study investigated the prognostic significance of RAS mutations and HER2 and COX2 proteins in colorectal cancer. Methods. Molecular analysis was performed using formalin-fixed, paraffin-embedded (FFPE) colorectal cancer samples. We analyzed full RAS mutation status using Sanger and pyrosequencing in 270 patients, while COX2 and HER2 protein expression were evaluated through immunohistochemistry. Survival analyses were performed using the Kaplan–Meier method and the log-rank test, with statistical analyses conducted using IBM SPSS Statistics version 21. Results Molecular profiling revealed RAS mutations in 40% of patients (35% KRAS, 4% NRAS), while protein expression analysis showed COX-2 and HER2 positivity in 82.9% and 2.9% of cases, respectively. Survival analyses demonstrated significantly poorer recurrence-free survival in patients with RAS mutations compared to RAS wild-type status (57% vs 95%, p < 0.001), particularly those with KRAS mutations (57% vs 94%, p < 0.001) and KRAS codon 13 mutations (p = 0.001). Overall survival was similarly diminished in patients with RAS mutations (78.18 vs. 104.29 months, P = 0.006), KRAS mutations (76.81 vs 104.14 months, P = 0.003), and high COX-2 expression (P = 0.04), with KRAS codon 13-mutated status emerging as the strongest negative prognostic indicator across all disease stages. Conclusion: These findings highlight the importance of molecular profiling in prognostic stratification and may inform treatment strategies for colorectal cancer patients. Citation Format: Fatima El Agy, Sara Boukansa, Laila Chbani. Prognostic value of RAS mutations, HER2, and COX2 expression in colon cancer: A large Moroccan cohort study [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr C043.