Journal of Pathology and Translational Medicine

Original Articles

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; Korean J Pathol. 2003;37(1):1-9.

Abstract PDF: 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.

MMP-2 and MMP-9 Expressions in Breast Carcinomas and Relationship with Major Prognostic Factors.: Hye Kyoung Yoon, Seol Mi Park; Korean J Pathol. 2004;38(2):79-85.

Abstract PDF: BACKGROUND
MMP-2 and MMP-9 are involved in the degradation of extracellular matrix, and MMP-2 and MMP-9 expressions in breast carcinomas have been reported as a poor prognostic factor. The aim of this study is to evaluate the prognostic value and the regulatory factors of MMP-2 and MMP-9 expressions in 73 cases of infiltrating ductal carcinomas, NOS type.
METHODS
Immunohistochemistry for MMP-1, -2, -3, -9 and TIMP-1, -2 were performed and evaluation for patient? age, size, histologic grade, lymph node metastasis and tumor markers such as ER, PR, p53, c-erbB-2, cathepsin D, MIB-1, and microvessel density was done.
RESULTS
The expression rates of MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1 and TIMP-2 were 74.0%, 76.7%, 1.4%, 87.7%, 24.7% and 75.3%, respectively. MMP-2 expression rate was higher in the tumors of low and intermediate grade and PR positive tumors (p<0.05), and MMP-9 expression showed an increasing tendency in ER positive tumor (p=0.0676). Positive relationships between MMP-2 and MMP-1 expressions, and MMP-9 and TIMP-2 expressions were recognized (p<0.05).
Conclusion
: The prognostic significance of MMP-2 and MMP-9 expressions is still unclear, and MMP-2 and MMP-9 expressions seemed to be positively related with MMP-1 and TIMP-2 expression, respectively.

Expression of MMP-2, MT1-MMP, and TIMP-2 mRNA in Breast Carcinomas.: Dong Won Kim, So Young Jin, Dong Wha Lee; Korean J Pathol. 2003;37(6):400-406.

Abstract PDF: BACKGROUND
The activation of proMMP-2 is induced by membrane type 1-matrix metalloproteinase (MT1-MMP), but inhibited by tissue inhibitors of matrix metalloproteinase type 2 (TIMP-2). This study was carried out to establish the pattern of mRNA expression of MMP-2, MT1-MMP, and TIMP-2 in breast carcinomas.
METHODS
Seventy-nine cases of invasive ductal carcinoma, 10 of ductal carcinoma in situ, and 10 of fibrocystic disease as a control were analysed for the expression of MMP-2, MT1-MMP, and TIMP-2 mRNA, using in situ hybridization. Correlations of the results with the clinical stage, tumor size, nodal status, and nuclear grade were analysed.
RESULTS
The expression rates of MMP-2, MT1-MMP, and TIMP-2 mRNA in invasive ductal carcinoma were 68%, 73%, and 56%, respectively. They were localized to both stromal and tumor cells, but mainly in the latter. The MMP-2 mRNA expression was significantly correlated with the clinical stage (p < 0.05), while the expression of TIMP-2 mRNA was inversely correlated with clinical stage and tumor size(p < 0.05). Significant positive correlations between MMP-2 and MT1-MMP expressions, along with inverse relationships between MMP-2 and TIMP-2, and between TIMP-2 and MT1-MMP, were also found. CONCLUSIONS: MMP-2 and TIMP-2 mRNA expressions might be useful as one of a range of prognostic parameters in breast carcinoma patients.

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