Immunohistochemical Study of Myofibroblasts in Normal Colonic Mucosa, Hyperplastic Polyps, and Adenomatous Colorectal Polyps

Abstract

Abstract Context.—Myofibroblasts are distinct cells with characteristics of both smooth muscle cells and fibroblasts. Through their ability to secrete cytokines, chemokines, prostaglandins, growth factors, and matrix components, they are thought to play critical roles in inflammation, growth, repair, and neoplasia. Objective.—The goal of this study was to identify the distinct cell populations of the lamina propria of normal colon and colorectal polyps. Design.—We studied the expression of α-smooth muscle actin (αSMA), smooth muscle myosin (SMM), desmin, vimentin, and c-kit by intestinal mesenchymal (stromal) cells in the normal colonic mucosa (n = 5), as well as in hyperplastic polyps (n = 5), sporadic colorectal adenomas (n = 47), and adenomas from patients with familial polyposis (n = 36). Results.—In the normal colonic mucosa, the pericryptal stromal cells were αSMA+, SMM+, desmin−, and vimentin+, defining them as myofibroblasts. In contrast, cells of the muscularis mucosae were αSMA+, SMM+, desmin+, and vimentin−, defining them as smooth muscle cells. α-Smooth muscle actin also highlighted direct connections between the muscularis mucosae and the pericryptal myofibroblasts, and vimentin immunostaining showed a network of connections between the αSMA+ pericryptal myofibroblasts and the αSMA− fibroblasts in the interstitium. In all hyperplastic polyps and adenomatous polyps, the interstitial stromal cells (fibroblasts) now also express αSMA and form a syncytium of αSMA+ networklike connections throughout the lamina propria. Stromal cells of sporadic adenomas demonstrated the same immunohistochemical staining characteristics displayed by adenomas from patients with familial polyposis and by hyperplastic polyps. Conclusions.—These findings indicate that in normal colon, αSMA− fibroblasts are the predominant cell type in the lamina propria. However, the pericryptal (subepithelial) stromal cells are a distinct cell type (αSMA+ myofibroblast) that is immunophenotypically different from muscularis mucosae smooth muscle cells and are connected to the interstitial, nonpericryptal fibroblasts with which they exist as a network throughout the lamina propria of the normal colon. Furthermore, in both hyperplastic and neoplastic polyps, there are changes in nonpericryptal fibroblasts from vimentin+, αSMA−, and SMM− to vimentin+, αSMA+, and SMM+; thus, the interstitial fibroblasts are replaced by myofibroblasts. The factors that cause these changes and the origin of the myofibroblasts need to be determined to clarify the biology of colorectal tumorigenesis.