Classification of molecularly distinct subtypes

We classified 24 SAC lesions into molecularly distinct subtypes by the immunohistochemistry analysis of CDX2, HTR2B, FRMD6, ZEB1, and MSI based on the methods described by Melo et al., who reported three main molecularly distinct subtypes of CRCs using an unsupervised classification strategy involving over 1100 individuals with colon cancer [18]. The three identified subtypes (CCS1, CCS2, and CCS3) were associated with chromosomal-instability (CIN), MSI, and BRAF mutant/ MSS, respectively. In the study by Melo et al., the CCS3 subtype is highly related to serrated adenomas. Moreover, these three subtypes can be easily classified using the immunohistochemistry findings and by the MSI analysis [18]. Therefore, we classified 24 SAC lesions into molecularly distinct subtypes by CDX2, HTR2B, FRMD6, and ZEB1 immunohistochemistry and the MSI analysis based on the methods of Melo et al. (CCS1: CDX2 positive, HTR2B negative, FRMD6 negative, ZEB1 negative, and MSS/MSI-L, CCS2: MSI-H, and CCS3: CDX2 negative, HTR2B positive, FRMD6 positive, ZEB1 positive, and MSS/MSI-L) [18].