Immunophenotypic Comparison of Neoplasms of the Appendix, Right Colon, and Left Colon in Search of a Site-Specific Phenotypic Signature

Aims. The proximal colon derives from the midgut endoderm, the distal one third derives from the hindgut endoderm, and the distal anal canal is of ectodermal origin. At least 5 molecular subtypes of colorectal carcinomas (CRC) have been identified, and some have a marked preferential right-sided location. Histologically, some CRC are much more common in the appendix. We hypothesized that these findings suggest the existence of diverse molecular genetic colonic subregions and compared the expression of classic and recently discovered colorectal markers in tumors at various locations to determine if a site-specific immunophenotypic signature could be identified. Methods and Results. Immunostains for CK7, CK20, MUC2, MUC5AC, MUC6, SATB2, DCR3/TNF6B, CDX2, Ki-67, and MMR proteins were performed on 17 appendiceal low-grade mucinous neoplasms and 6 crypt cell adenocarcinomas of the appendix, 15 right-sided and 15 left-sided mucinous adenocarcinomas, 17 right-sided and 15 left-sided conventional adenocarcinomas, and 5 signet ring cell adenocarcinomas (SRCCA). Statistically significant differences in the expression of MUC2, MUC5AC, MUC6, CK7, and SATB2 by site and/or histologic type were documented. MMR deficiency showed a significant correlation with MUC5AC and MUC6 expression. DCR3, CDX2, and CK20 expression was consistent throughout the colon. A CK7+/CK20+ phenotype was most common in appendiceal tumors and SRCCA. Conclusions. Statistically significant differences in the expression of some markers by histologic type and site were documented, supporting the existence of regional molecular genetic heterogeneity in the colon that result in site-specific epigenetic susceptibilities, tumor phenotypes, and immunophenotypes.