Mucosal remodeling in long-standing ulcerative colitis with colorectal neoplasia: significant alterations of NCAM+ or alpha-SMA+ subepithelial myofibroblasts and interstitial cells.
Evidence has been provided in ulcerative colitis (UC) that early genomic instability of both epithelial and stromal cells is important for colorectal tumorigenesis, as well as remodeling and morphological alterations of mucosal crypts. To clarify roles of stromal cells in tumor development in UC, the present study focused on heterogeneous phenotypes of subepithelial myofibroblasts and interstitial cells, in association with mucosal remodeling. To clarify the relationship of alterations to tumorigenesis, mucosa of resected rectae from patients with UC (n= 49) and sporadic cancer (n= 10) were analyzed on immunohistochemistry and also on immunoelectron microscopy. Heterogeneous phenotypes of neural cell adhesion molecule (NCAM)+ and/or alpha-smooth muscle actin (alpha-SMA)+ subepithelial myofibroblasts and interstitial cells were demonstrated, corresponding to colonic stellate cells. Decrease of NCAM+ subepithelial myofibroblasts and interstitial cells, and increase of alpha-SMA+ interstitial cells were significant in UC with neoplasia as compared to without neoplasia. alpha-SMA+ muscularis mucosae was significantly more thickened in tumor cases. Deposits of Masson's trichrome+ and type III and I collagen in the muscularis mucosae and lamina propria appeared to increase in relation to the numbers of alpha-SMA+ interstitial cells. Mucosal remodeling with alterations of NCAM+ or alpha-SMA+ subepithelial and interstitial cells may play a critical role in UC-associated tumorigenesis.
Department of Pathology, Kitasato University, Kanagawa, Japan. isaokaya@med.kitasato-u.ac.jp
Isao
I
Okayasu
Tsutomu
T
Yoshida
Tetuo
T
Mikami
Kiyomi
K
Hana
Masashi
M
Yokozawa
Kayo
K
Araki
Jun
J
Mitsuhashi
Masaomi
M
Kikuchi
Eijiro
E
Adachi
Miwa
M
Sada
D000199:Actins / Q000378:metabolism*; D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007124:Immunoenzyme Techniques; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000601:surgery; D008297:Male; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism / Q000648:ultrastructure; D055815:Young Adult
C541116:ACTA2 protein, human; D000199:Actins; D014408:Biomarkers, Tumor; D019006:Neural Cell Adhesion Molecules