Ectopic Gastric and Intestinal Phenotypes, Neuroendocrine Cell Differentiation, and SOX2 Expression Correlated With Early Tumor Progression in Colorectal Laterally Spreading Tumors

Abstract Introduction The significance of the ectopic gastric phenotype remains unclear in patients with colorectal laterally spreading tumors (LSTs). We investigated clinicopathologic differences among LST subtypes, aiming to identify factors indicative of malignant transformation and invasion that are linked to ectopic gastric phenotype and tumor progression. Materials and Methods We analyzed the morphologic characteristics of 105 colorectal LSTs resected by endoscopic submucosal dissection. LSTs were classified into 2 subtypes: granular (G-LST) and nongranular (NG-LST). Resected LSTs were analyzed histologically and were immunohistochemically stained for MUC5AC, MUC6 , chromogranin A, CD10, and SOX2 . Results The 105 LSTs included 60 G-LSTs and 45 NG-LSTs. By histology, G-LSTs comprised 5 adenomas with low-grade dysplasia (LAs), 45 adenomas with high-grade dysplasia (HAs), and 10 adenocarcinomas invading the submucosa (SMs). NG-LSTs comprised 8 LAs, 25 HAs, and 12 SMs. MUC5AC positivity was significantly higher in G-LSTs compared to NG-LSTs ( P  = .002), and MUC5AC positivity in HA lesions was significantly higher than in LA lesions ( P  = .01). MUC6 and SOX2 positivity in SM G-LSTs, and chromogranin A positivity in SM NG-LSTs were significantly higher than in HAs ( P  = .01, .01, and .03, respectively). CD10 positivity in SM NG-LSTs was significantly higher than in HAs and LAs ( P  = .02 and .01, respectively). Conclusion Ectopic gastric and intestinal phenotypes, neuroendocrine cell differentiation, and SOX2 expression differ according to tumor grade in colorectal LSTs, and these markers are correlated with early tumor progression in each LST subtype.