Immunohistochemical study of myofibroblasts in normal colonic mucosa, hyperplastic polyps, and adenomatous colorectal polyps.
BACKGROUND
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.


METHODS
We studied the expression of alpha-smooth muscle actin (alphaSMA), 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 alphaSMA+, SMM+, desmin-, and vimentin+, defining them as myofibroblasts. In contrast, cells of the muscularis mucosae were alphaSMA+, SMM+, desmin+, and vimentin-, defining them as smooth muscle cells. alpha-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 alphaSMA+ pericryptal myofibroblasts and the alphaSMA- fibroblasts in the interstitium. In all hyperplastic polyps and adenomatous polyps, the interstitial stromal cells (fibroblasts) now also express alphaSMA and form a syncytium of alphaSMA+ 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, alphaSMA- fibroblasts are the predominant cell type in the lamina propria. However, the pericryptal (subepithelial) stromal cells are a distinct cell type (alphaSMA+ 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+, alphaSMA-, and SMM- to vimentin+, alphaSMA+, 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.
Adegboyega
Patrick A
PA
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA. paadegbo@utmb.edu
Mifflin
Randy C
RC
DiMari
John F
JF
Saada
Jamal I
JI
Powell
Don W
DW
D000236:Adenoma / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D011125:Adenomatous Polyposis Coli / Q000150:complications / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006965:Hyperplasia / Q000473:pathology; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000033:anatomy & histology / Q000378:metabolism* / Q000473:pathology; D007417:Intestinal Polyps / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins