Increased membrane type 1 matrix metalloproteinase expression from adenoma to colon cancer: A possible mechanism of neoplastic progression

Sandeep Malhotra, Elliot Newman, David Eisenberg, John Scholes, Rosemary Wieczorek, Paolo Mignatti, Peter Shamamian

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

PURPOSE: 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.

Original languageEnglish (US)
Pages (from-to)537-543
Number of pages7
JournalDiseases of the Colon and Rectum
Volume45
Issue number4
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Matrix Metalloproteinase 14
Adenoma
Colonic Neoplasms
Carcinoma in Situ
Staining and Labeling
Mucous Membrane
Membrane-Associated Matrix Metalloproteinases
Colonic Polyps
Recurrence
Matrix Metalloproteinase 2
Basement Membrane
Blood Vessels
Neoplasms
Colon
Adenocarcinoma
Monoclonal Antibodies
Carcinoma

Keywords

  • Colon cancer
  • Colonic polyps
  • Membrane type 1 matrix metalloproteinase
  • Metalloproteinase

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Increased membrane type 1 matrix metalloproteinase expression from adenoma to colon cancer : A possible mechanism of neoplastic progression. / Malhotra, Sandeep; Newman, Elliot; Eisenberg, David; Scholes, John; Wieczorek, Rosemary; Mignatti, Paolo; Shamamian, Peter.

In: Diseases of the Colon and Rectum, Vol. 45, No. 4, 2002, p. 537-543.

Research output: Contribution to journalArticle

Malhotra, Sandeep ; Newman, Elliot ; Eisenberg, David ; Scholes, John ; Wieczorek, Rosemary ; Mignatti, Paolo ; Shamamian, Peter. / Increased membrane type 1 matrix metalloproteinase expression from adenoma to colon cancer : A possible mechanism of neoplastic progression. In: Diseases of the Colon and Rectum. 2002 ; Vol. 45, No. 4. pp. 537-543.
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T1 - Increased membrane type 1 matrix metalloproteinase expression from adenoma to colon cancer

T2 - A possible mechanism of neoplastic progression

AU - Malhotra, Sandeep

AU - Newman, Elliot

AU - Eisenberg, David

AU - Scholes, John

AU - Wieczorek, Rosemary

AU - Mignatti, Paolo

AU - Shamamian, Peter

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N2 - PURPOSE: 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.

AB - PURPOSE: 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.

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