Matrix Metalloproteinases's Expression In The Different Components Of The Human IDC And Its Clinical Significance

Breast carcinoma (BC) is a most common female carcinoma. Its morbility is 31% and the mortality is only second to the lung carcinoma. The infitrating ductal carcinoma (IDC) is the most important type of BC. Broad metastasis, function failure of many internal organs and the cachexia are the major reasons of the death resulted from breast carcinoma.Extra cellular matrix (ECM) plays a key role in the prevention of invasion and metastasis of the tumor. Matrix metalloproteinase (MMPs) can degrade the components of ECM and enhance the invasion and metastasis of the tumor. MMP-2, but not the other members of the family, specifically degrades the structural protein of the basement membrane (BM), the type IV collagen. The expression of MMP-2 was increased in the estrogen dependant tumors, such as the breast and ovary carcinoma. The level of MMP-2 is correlated with the abilities of invasion and degree of malignancy of the tumors. MMP-7, another member of the family, as matrilysin, functions in the tumor angiogenesis with its ability of protein degeneration and generally substrate specificity. It is shown that MMP-7 expressed in many tumor tissues, and the level is closely correlated with the tumor growth, development, and metastasis through lymphatic and blood vessels. The researches in MMP-7 and combination with the clinical therapy are important to the knowledge of metastasis and invasion of tumor, to pursuetargeted and effective therapy.The expression levels of MMP-2 and MMP-7 genes were estimated based on the protein and mRNA products. Laser microdissection(LMD) technique was used to separate texture and stoma of breast carcinoma tissues to explore the effects and importance of the two members on metastasis and invasion of the breast carcinomas. MMP-2 and MMP-7 mRNAs were amplified by RT-PCR based on the RNAs purified from different parts of the breast carcinomas. The immunohistochemistry staining technique was used to view the expression of two genes in protein level.The results from immunohistochemistry indicated MMP-2 and MMP-7 protein expression is positive in tumor endochylema and small quantity stroma. The positive rates of MMP-2 and MMP-7 in 37 breast carcinoma tissues were 70.3 % (21/ 37) and 75.7 % (28/37). There are significant difference of the expressions of MMP-2 and MMP-7 among different histological grading (P<0.05). The expression of MMP-2 and MMP-7 had no correlations with the other clinic pathological features (P>0.05).(Semi-quantitive) RT-PCR analysis show that the levels of MMP-2 and MMP-7 mRNAs was significant higher in the breast tumor than those in normal breast tissues. The expression of MMP-2 and MMP-7 in histological grades(II, III) of the homogenate of the tumors is significantly higher than in grade I, and there were no statistically significant between grades II, III (P>0.05). Laser micro dissection was used to separate texture of tumors and the mRNAs of MMP-2 and MMP-7 in the separated samples were analyzed by RT-PCR. The expression of MMP-2 and MMP-7 mRNAs was highest in histological grade II of the tomour, text to grade III and last one is grade I, The levels in grades II, IIIare significant higher than that in grade I (P <0.01). The levels of MMP-2 and MMP-7 messenger in the invasive ductal carcinoma are correlated with the metastasis of the lymph. MMP-2 and MMP-7 mRNAs were expressed in significantly higher levels in the parenchyma tissues of the tumors with metastasis in lymph node than those without lymph metastasis (p<0.01). Our results display that the expression level of MMP-2 and MMP-7 in tumor cell is derangement with tumor tissue, it can provide new target for diagnosis of breast carcinoma metastasis and prognosis evaluation.