Do Colorectal Serrated and Non-Serrated Adenocarcinomas Differ in Somatic Mutations and Clinicopathologic Features?

<i>Background and Objectives</i>: Serrated adenocarcinoma (SAC) is a distinctive neoplasm that is histopathologically characterized by the presence of epithelial serration, an eosinophilic cytoplasm, and a vesicular nucleus. However, the literature data concerning somatic mutations in SACs remain extremely limited. <i>Materials and Methods</i>: A total of 159 colon resection cases diagnosed with adenocarcinoma whose DNA mutations were analyzed by next-generation sequencing (NGS) were retrospectively reviewed. In 23 cases, the SAC area exceeded 50%. A chi-square test was used to evaluate histopathologic characteristics and somatic mutations in SACs and non-serrated adenocarcinomas (non-SACs). <i>Results</i>: A significant difference was found in histological grade (<i>p</i> = 0.019) between SACs and non-SACs. <i>TP53</i>, <i>KRAS</i>, and <i>PIK3CA</i> genes have been identified as the most frequently mutated genes in both SACs and non-SACs. No statistically significant difference in somatic mutations was observed between the two groups (<i>p</i> > 0.05). <i>Conclusions</i>: In the present study, a higher prevalence of <i>KRAS</i> mutations was observed in SACs compared to <i>BRAF</i> mutations (<i>KRAS</i>: 39.1%, <i>BRAF</i>: 4.3%). This finding is consistent with the recent literature reporting a higher prevalence of <i>KRAS</i> mutations in colorectal SACs, in contrast to previous studies. The somatic mutation results of our study and the previous literature data suggest the potential importance of epigenetic alterations documented in the literature in the development of SACs.