Association of KRAS Mutation with Clinicopathological Variables in Colorectal Carcinomas: An Observational Cross-sectional Study

Introduction: Colorectal carcinoma is one of the most common malignancies worldwide. The development of carcinoma occurs as a multistep process involving a wide variety of genetic alterations, among which Kirsten Rat Sarcoma (KRAS) mutations play a pivotal role in increasing proliferation and decreasing apoptosis of tumour cells. Aim: To determine the incidence of KRAS mutations in colorectal carcinomas and establish associations with age, histopathological findings such as tumour site, size, angiolymphatic invasion, lymph node status, and staging of carcinoma. Materials and Methods: A cross-sectional analytical observational study was conducted in the Pathology Department of Rajiv Gandhi Government General hospital, Chennai in Tamil Nadu, South India, on colorectal carcinoma biopsy samples. Over a study period of two years, from January 2022 to December 2024, 30 tissue samples of colorectal carcinoma were collected. Formalin-fixed paraffin-embedded blocks of these samples were subjected to molecular KRAS mutational analysis at codons 12 and 13 of exon 2 through Polymerase Chain Reaction (PCR), followed by Sanger sequencing. The incidence of KRAS mutations and their concurrent association with histopathological variables such as age, tumour site, size, angiolymphatic invasion, lymph node status, and staging of carcinoma were studied. Statistical evaluations were performed using International Business Machine (IBM)-Statistical Packages for Social Sciences (SPSS) version 20.0. Pearson’s Chi-squared test was utilised to analyse the association between variables. Results: The mean age of presentation in the study was 55.2±13.95 years. Out of 250 colorectal adenocarcinoma biopsy samples examined, 30 adequate samples were extracted. Of these, 27 were conventional adenocarcinomas and 3 were mucinous carcinomas with moderate differentiation. The sample included 17 males and 13 females. KRAS mutations were seen in 5 (16.7%) samples of patients older than 50 years. There was no statistically significant association between the incidence of KRAS mutations and age (p=0.686), gender (p=0.410), histopathological findings such as tumour site (p=0.807), size (p=0.828), angiolymphatic invasion (p=0.787), lymph node status (p=0.640), and staging of carcinoma (p=0.730); nevertheless, their importance should not be undermined. Conclusion: The KRAS mutations, commonly observed in codons 12 and 13 of exon 2, are involved in the multistep tumourigenesis of colorectal carcinoma. These mutations contribute to tumour aggressiveness, favoring metastasis and reducing apoptosis, thereby being associated with poor survival outcomes for patients. KRAS mutations are predictive of resistance to anti-EGFR targeted therapies, highlighting the necessity of analysing them in all cases of colorectal carcinoma to develop effective screening strategies and management plans.