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The Korean Journal of Pathology 2003;37(1): 1-9.
Expression of Matrix Metalloproteinase (MMP)-2, MMP-9, Tissue Inhibitor of Metalloproteinase (TIMP)-1 and TIMP-2 in Adenocarcinomas of The Gallbladder.
Jong Yup Bae, Jinsub Choi, Hyun Cheol Chung, Chanil Park, Young Nyun Park
1Department of Pathology, Kumi CHA Hospital, College of Medicine, Pochon CHA University, Kumi, Korea.
2Department of General Surgery, Cancer Metastasis Research Center, Yonsei Cancer Center, Korea.
3Department of Pathology, College of Medicine, Brain Korea 21 Project for Medical Science, Yonsei University, Seoul, Korea. young0608@yumc.yonsei.ac.kr
BACKGROUND: Matrix metalloproteinase (MMP)-2 and MMP-9 degrade type IV collagen and are antagonized by the tissue inhibitors of metalloproteinase (TIMP)-2 and TIMP-1, respectively. METHODS: We studied by immunohistochemistry the expressions of MMP-2, MMP-9, TIMP-1 and TIMP-2 in 72 cases of adenocarcinoma of the gallbladder. RESULTS: The MMP-2, MMP-9 and TIMP-1 expressions were significantly higher in well/moderately differentiated adenocarcinomas than in poorly differentiated adenocarcinomas, in adenocarcinomas that had invaded the lamina propria/proper muscle than in those that had invaded the perimuscular connective tissue or beyond the serosa, and in adenocarcinomas with fungating growth than in those with infiltrative growth. The TIMP-2 expression showed a similar pattern without statistical significance. Regarding the status of lymph node metastasis, the MMP-2 expression was significantly higher in cases without lymph node metastasis. The MMP-2 and MMP-9 expressions were significantly related to those of TIMP-2 and TIMP-1, respectively, with regard to depth of invasion, differentiation, and growth patterns of the adenocarcinomas. CONCLUSIONS: MMP-2, MMP-9, TIMP-1 and TIMP-2 are suggested to play important roles in the progression to early invasion of adenocarcinomas, in which the function of MMP-2 is inhibited by TIMP-2.
Key Words: Gallbladder Neoplasms; Matrix Metalloproteinases; Tissue Inhibitor of Metalloproteinases; Immunohistochemistry