KRAS and PIK3CA mutations in colorectal adenocarcinomas correlate with aggressive histological features and behavior

Abstract

Tumor budding (TB) in colorectal carcinoma (CRC) is related to epithelial-mesenchymal transition and has been recently characterized as an indicator of poor prognosis along with lymphovascular tumor emboli, perineural invasion, and an infiltrative growth pattern. Mutations in the genes of the Ras-mitogen-activated protein kinase and phosphatidylinositol-4,5-bisphosphate 3-kinase pathways are associated with epithelial-mesenchymal transition and an aggressive CRC phenotype and have been used in patient stratification for anti-epidermal growth factor receptor therapies; however, the impact of these mutations on CRC morphology and behavior remains unclear. In this study, using a multigene panel, we detected KRAS, NRAS, BRAF, PIK3CA, TP53, and POLE mutations in 90 CRCs and investigated their associations with clinicopathological parameters, including TB. Our results showed that 21 of 34 tumors with high-grade TB had KRAS mutations (P=.001) and KRAS G12D and PIK3CA exon 9 variants were significantly associated with high-grade TB (P=.002 and .006, respectively); furthermore, tumors with KRAS mutations in exons 3 and 4 tended to have lymphovascular tumor emboli and perineural invasion (P=.044 and .049, respectively). PIK3CA exon 9 mutations indicated a tendency for shorter disease-free survival (P=.030), whereas BRAF mutations were associated with extracellular mucin deposition (P=.016). Our study revealed a correlation of KRAS mutations with high-grade TB, an association of certain KRAS and PIK3CA variants with aggressive clinicopathological features, as well as a possible relationship between BRAF mutations and mucin production in CRC.