Matrix metalloproteinases and tissue inhibitors of metalloproteinases in colonic adenomas-adenocarcinomas.
Colonic adenocarcinomas evolve through a multistep process from tubular adenomas to invasive adenocarcinomas. Matrix metalloproteinases (MMPs) have been implicated in proteolysis of basement membrane for initiation of metastatic cascade.


METHODS
By immunocytochemical staining, hyperplastic polyps, tubular adenomas, tubovillous adenomas, villous adenomas to adenocarcinomas were systematically examined for the presence of MMP-2 (gelatinase A) and MMP-9 (gelatinase B) and tissue inhibitor of MMP (TIMP)-1 and TIMP-2, respectively.


RESULTS
MMP-2 and MMP-9, and TIMP-1 and TIMP-2 were immunolocalized in scattered stromal cells, whereas epithelial cells of normal mucosa and hyperplastic polyps were weakly stained. From tubular adenomas to villous adenomas, immunolocalization of gelatinases and TIMPs showed increasing gradually, and in situ carcinomas showed a definite positive, immunolocalization of gelatinases and TIMPs.


CONCLUSIONS
Increasing immunolocalization of gelatinases and TIMPs from tubular adenomas to adenocarcinomas coincides with a multistep process of colonic tumorigenesis.
Tomita
T
T
Department of Pathology, University of Kansas Medical Center, Kansas City 66160, USA.
Iwata
K
K
D000230:Adenocarcinoma / Q000201:enzymology* / Q000378:metabolism; D000236:Adenoma / Q000201:enzymology* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000378:metabolism; D003111:Colonic Polyps / Q000201:enzymology; D005109:Extracellular Matrix / Q000201:enzymology; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008666:Metalloendopeptidases / Q000378:metabolism*; D008875:Middle Aged; D011480:Protease Inhibitors / Q000378:metabolism*; D019714:Tissue Inhibitor of Metalloproteinases
D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D011480:Protease Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D008666:Metalloendopeptidases