Prognostic impact of histological categorisation of epithelial-mesenchymal transition in colorectal cancer

Abstract

Background: The crosstalk between cancer cells and stroma is involved in the acquired capability for metastasis through the induction of epithelial-mesenchymal transition (EMT). We aimed to clarify the prognostic value of the histological category of EMT in colorectal cancer (CRC). Methods: Tumour EMT was graded into one of three histological categories on the basis of integrated assessment of poorly differentiated clusters and pro-EMT desmoplasia at the leading edge of the primary tumour (HistologyEMT). Stage II and III CRC patients (cohort 1, N=500) and stage IV patients (cohort 2, N=196) were retrospectively analysed. Results: In cohort 1, patients were stratified into three groups with widely different disease-free survival rates (95%, 83% and 39%) on the basis of HistologyEMT (P<0.0001). In cohort 2, HistologyEMT significantly stratified overall survival of patients irrespective of metasectomy. Multivariate analyses indicated that HistologyEMT had a strong prognostic impact independent of staging factors. Statistically, HistologyEMT had a better prognostic stratification power than T and N stages; however, in cohort 2, the power of M substage was superior. Conclusions: A histological model to categorise EMT by integrated assessment of dedifferentiation and desmoplastic environment is a potent prognostic index independent of staging factors.