Histologic Categorization of Desmoplastic Reaction: Its Relevance to the Colorectal Cancer Microenvironment and Prognosis

Although the essential roles of stromata in tumor development have been recognized, the morphologic classification of desmoplastic reaction (DR) in colorectal cancer (CRC) is unclear. In this study, DRs were histologically classified into three patterns based on the products of activated fibroblasts (i.e., keloid-like collagen and myxoid stroma). The prognostic impact of DRs was evaluated in two independent cohorts of stages 2 and 3 CRC patients: cohort 1 (880 patients) and cohort 2 (474 patients). The association of DR and the local environment was investigated immunohistochemically. In cohort 1, mature DR was shown by 413 patients, intermediate DR by 275 patients, and immature DR by 192 patients. Categorization of DR was significantly associated with tumor location, pT and pN stages, tumor differentiation, venous invasion, tumor budding, and Crohn’s-like lymphoid reaction (P ≤ 0.0001–0.008). Immature DR was relevant to the high incidence of recurrence in the liver, lung, lymph nodes, peritoneum, and locoregional areas (P ≤ 0.0001–0.002). The 5-year disease-free survival rate was highest in the mature group (87 %), followed by the intermediate group (72 %) and the immature group (49 % (P