Epithelial-Mesenchymal Transition and Somatic Alteration in Colorectal Cancer with and without Peritoneal Carcinomatosis

Colorectal cancer is highly metastatic even when the tumors are small. To disseminate, cells use a complex and multistage process known as the epithelial-mesenchymal transition, in which epithelial phenotype is transformed into mesenchymal phenotype. The objective of this study is to describe the epithelial-mesenchymal transition in terms of gene expression profile and somatic alterations in samples of colorectal cancer with or without peritoneal carcinomatosis. We analyzed samples taken from 38 patients with colorectal cancer (stages II-IV) and samples from 20 patients with colorectal cancer complicated by peritoneal carcinomatosis. The expression of ZEB1, ZEB2, CDH1, VIM, and SNAI1 was analyzed by real-time PCR. KRAS/BRAF mutations were mapped using sequencing. Microsatellite instability was evaluated by fragment analysis. Epithelial-mesenchymal transition was detected in 6 out of 38 samples of colorectal cancer (stages II-IV), 7 out of 20 tumors from patients with peritoneal carcinomatosis, and 19 out of 20 samples taken from carcinomatous nodules. Tumors of the mesenchymal subtype displayed high frequency of somatic mutations, microsatellite stability, and low degree of differentiation. The identification of epithelial-mesenchymal transition may be used as a marker of high metastatic potential, which is particularly relevant at early stages of tumor growth.