A Novel Colorectal Cancer Profile in a Large Population of Romania: The Coexistence of MSI Status with KRAS or NRAS Mutations in Patients with Colorectal Cancer

Colorectal cancer is one of the most prevalent malignancies worldwide, ranking third globally and second in Romania. This study aimed to investigate the coexist-ence of microsatellite instability (MSI) status with KRAS and NRAS mutations in colorectal cancer patients. Methods: We analyzed clinicopathological characteristics in 120 patients diagnosed with colorectal cancer. PCR techniques were used to assess MSI status and detect KRAS and NRAS mutations. Results: Among the 120 patients, KRAS mutations were detected in 86.7%, while NRAS mutations were identified in 12.5% of cases. Mismatch repair-proficient (pMMR)/microsatellite stable (MSS) sta-tus was observed in 95% of cases, coexisting with KRAS or NRAS mutations. A sig-nificant association was found between tumor localization and the presence of KRAS or NRAS mutations in MSS cases, with a predisposition for rectal cancer (p = 0.015). Given the high frequency of KRAS mutations and the predominance of MSS status, we evaluated their statistical association, yielding a highly significant result (p = 0.0001). Conclusions: These findings suggest that KRAS mutations, in combina-tion with pMMR status, may define a distinct molecular subtype of colorectal cancer with unique clinicopathological features. Further research is essential to understand its impact on tumor biology, therapeutic response, and survival outcomes.