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Analysis of MT1‐MMP and MMP2 expression in human gastric cancers
Author(s) -
Mori Masaki,
Mimori Koshi,
Shiraishi Takeshi,
Fujie Tatsuo,
Baba Kinya,
Kusumoto Hiroki,
Haraguchi Masaru,
Ueo Hiroaki,
Akiyoshi Tsuyoshi
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19970620)74:3<316::aid-ijc14>3.0.co;2-9
Subject(s) - mmp2 , immunohistochemistry , matrix metalloproteinase , pathology , metastasis , tissue microarray , lymph node , medicine , gelatinase a , cancer research , biology , cancer
Membrane‐type 1 matrix metalloproteinase (MT1‐MMP) is a presumed activator of MMP2, which is one of the major proteinases in tumor cell invasion. In this study, we determined the clinico‐pathologic significance of MT1‐MMP expression in 68 human gastric carcinomas. The tumor‐normal ratio (T/N ratio) of MT1‐MMP expression was determined by reverse transcription‐polymerase chain reaction analysis. To visualize the localization of MT1‐MMP, an immunohistochemical study was performed. In addition, a gelatin zymography was done to examine the activation ratio of MMP2, and a correlation between MT1‐MMP expression and activation of MMP2 was studied. The expression of MT1‐MMP mRNA was higher in tumor tissue than in corresponding normal tissue in most cases. The mean value of the T/N ratio was 4.8. Twenty cases with T/N ≥ 4.8 showed significantly deeper invasion and higher frequency of lymph node metastasis than 48 cases with T/N < 4.8. MT1‐MMP expression was an independent factor influencing both tumor invasion of the gastric wall and lymph node metastasis. Although MT1‐MMP expression was not an independent prognostic factor, the patients with T/N ≥ 4.8 showed a significantly worse prognosis than those with T/N < 4.8. An immunohistochemical study demonstrated that MT1‐MMP expression was mainly recognized in the tumor cells. There was a significant correlation between MT1‐MMP expression and activation of MMP2. Our findings suggest that: 1) the expression of MT1‐MMP may influence prognosis via tumor invasion of the gastric wall and lymph node metastasis, and 2) MT1‐MMP activation of MMP2 may be clinically relevant in gastric carcinoma tumors. Int. J. Cancer 74:316‐321, 1997. © 1997 Wiley‐Liss, Inc.