Korean J Gastroenterol.  2005 Jun;45(6):401-408.

The Expression of Matrix Metalloproteinases (MMPs), Tissue Inhibitor of Metalloproteinases (TIMPs) and Angiogenesis in Relation to the Depth of Tumor Invasion and Lymph Node Metastasis in Submucosally Invasive Colorectal Carcinoma

Affiliations
  • 1Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea.
  • 2Ewha Womans University College of Medicine, Ewha Medical Research Institute, Seoul, Korea.
  • 3Departments of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. sky@amc.seoul.kr
  • 4Departments of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
  • 5Departments of Diagnostic Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
  • 6Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

Abstract

BACKGROUND/AIMS: Lymph node (LN) metastasis occurs in approximately 10% of patients with submucosally invasive colorectal carcinoma. This study was performed to determine the role of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs) production and microvessel formation on the LN metastasis in submucosally invasive colorectal carcinoma. METHODS: A total of forty-one subjects with surgically resected submucosally invasive colorectal carcinoma were included in this study. Immunohistochemical staining of MMP-2, MMP-9, TIMP-1, TIMP-2, and urokinase-type plasminogen activator were performed. Angiogenesis was evaluated by counting the number of microvessels in each pathologic specimen as identified by CD34 immunohistochemical staining. RESULTS: The depth of submucosal invasion was not significantly correlated with the expression of MMP-2, MMP-9, TIMP-1, TIMP-2, or urokinase-type plasminogen activator, but the microvessel count was significantly correlated with the absolute depth of invasion (r=0.312, p<0.05). Upregulation of TIMP-2 was positively correlated with adjacent lymphatic invasion (p<0.05) and increased TIMP-2 expression was correlated with LN metastasis in submucosally invasive colorectal carcinoma (p=0.088). CONCLUSIONS: These results suggest that the expression of TIMP-2 and the microvessel count may be useful parameters for considering additional surgery after endoscopic treatment of submucosally invasive colorectal carcinoma.

Keyword

Endoscopic treatment; Submucosally invasive colorectal cancer; Matrix metalloproteinases; Angiogenesis

MeSH Terms

Adult
Aged
Aged, 80 and over
Colorectal Neoplasms/blood supply/*metabolism/pathology
Female
Humans
Immunohistochemistry
Lymphatic Metastasis
Male
Matrix Metalloproteinases/*metabolism
Middle Aged
Neoplasm Invasiveness
Neovascularization, Pathologic/*pathology
Tissue Inhibitor of Metalloproteinases/*metabolism
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