Increased membrane type 1 matrix metalloproteinase expression from adenoma to colon cancer: a possible mechanism of neoplastic progression.
OBJECTIVE
Membrane type 1 matrix metalloproteinase is a membrane-associated matrix metalloproteinase central to the degradation of basement membrane components via the activation of matrix metalloproteinase-2. Although membrane type 1 matrix metalloproteinase is overexpressed in invasive colon cancer, its expression in colonic polyps and carcinoma in situ has not been defined. In addition, the association of membrane type 1 matrix metalloproteinase expression by a primary tumor and recurrence of colon cancers has not been examined.


METHODS
Immunoperoxidase staining was performed on randomly selected specimens containing adenoma (n = 17), carcinoma in situ (n = 9), or metastatic colon carcinoma (n = 8) with mouse monoclonal antibody to human membrane type 1 matrix metalloproteinase. Similar staining was also performed on randomly selected node-negative colon cancers that recurred within five years of resection (n = 17), matched for age, gender, stage, grade, and vascular, lymphatic, and perineural invasion, and node-negative colon cancers that did not recur within five years of resection (n = 17). Staining for membrane type 1 matrix metalloproteinase was graded. Mean scores for the groups were compared by Wilcoxon test.


RESULTS
We found a progressive and significant increase in the mean score of membrane type 1 matrix metalloproteinase from normal mucosa to adenoma (P < 0.001), carcinoma in situ (P < 0.006), and invasive cancer (P < 0.009). However, there was no difference in membrane type 1 matrix metalloproteinase expression between the recurrent and nonrecurrent groups of node-negative colon cancer (P = not significant).


CONCLUSIONS
These data suggest that membrane type 1 matrix metalloproteinase expression increases with progression from normal mucosa to invasive adenocarcinoma; however, it cannot be used as a prognostic indicator on which adjuvant therapy is based in node-negative colon cancer because of its failure to predict recurrence in this patient group.
Malhotra
Sandeep
S
Department of Surgery, S. Arthur Localio Laboratory for Surgical Research, New York University School of Medicine, New York, New York, USA.
Newman
Elliot
E
Eisenberg
David
D
Scholes
John
J
Wieczorek
Rosemary
R
Mignatti
Paolo
P
Shamamian
Peter
P
D000236:Adenoma / Q000201:enzymology* / Q000473:pathology* / Q000503:physiopathology; D002278:Carcinoma in Situ / Q000201:enzymology* / Q000473:pathology* / Q000503:physiopathology; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000473:pathology* / Q000503:physiopathology; D018450:Disease Progression; D006801:Humans; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000032:analysis*; D009364:Neoplasm Recurrence, Local / Q000201:enzymology* / Q000473:pathology* / Q000503:physiopathology; D011237:Predictive Value of Tests; D011379:Prognosis; D011897:Random Allocation; D013194:Staining and Labeling
D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases