The Expression And Significance Of MMP-2and TIMP-2in Benign And Malignant Prostatic Lesions

Background and Objective:In china, prostate cancer (PC) is the most common malignant neoplasm in rinary system. The proportion of PC is9.7%.in different countries and regions, the morbidity and mortality of PC are very different, among developed countries is15.3%, however, in developing countries the date is4.3%. With increase of aging population, the incidence of PC has been on the rise over years. In general, domestic fatality rate is higher. The key of reducing the mortality lies in the early diagnosis and early treatment. So early discovery, early diagnosis and early treatment is significantly importent. Matrix metalloproteinases (MMPs) are more important family of proteolytic enzymes, which are capable of degradation of the Proteins composing the extracellular matrix and basement membrane.Tissue inhibitors of metalloproteinase(TIMPs) are MMPs’natural inhibitors.We aim to researching the different expression and the clinical significance of matrix metalloproteinase-2(MMP-2) and tissue inhibitor of metalloproteinase-2(TIMP-2) in benign and malignant prostaticlesions. Disscussing the clinical significance of MMP-2and TIMP-2in the malignant transformation of prostatic epithelium.Materials and Method:A total of98patients from department of urology, second hospital of Tianjin medical university, containing20cases of benign prostatic hyperplasia (BPH),20cases of prostatic intraepithelial neoplasia (PIN) and58cases of prostatic carcinoma (PC), with accession from June2007through February2012, were included in this study.SABC immunohistochemical analysis was used to determine the expression levels of MMP-2and TIMP-2in20cases of BPH,20cases of PIN and58cases of PC. According to the grade classification of Gleason scales, G1+G2(2-6scores)14cases, G3+G4(7-10scores)44cases, we choose positive breast cancer histological section as positive control, with PBS replaced the antibody as negative control. The results were observed by light microscope, and buffy particles in cells were considered as positive cases. SPSS19.0software application was used for all analysis and statistical significance was defined as P values less than0.05.Results:(1) MMP-2is mainly distributed in the secretary cell of the normal prostate tissue. The expression of MMP-2was the least in BPH and significantly higher in PIN compared to PC (P<0.05). The expression of MMP-2in PC was significant difference in clinical classification and pathological grade (P<0.05). In addition, MMP-2protein expression in prostatic carcinoma was posatively correlated with tumor stage and histological grade (P<0.05);(2) TIMP-2is mainly distributed in the three groups (BPH,PIN,PC) glandular epithelium basal cell cytoplasmic, visible point and flaky distribution. The expression of TIMP-2was the highest in PC and significantly higher in PIN compared to BPH (P<0.05). The expression of TIMP-2in PC was significant difference in clinical classification and pathological grade (P<0.05). In addition, TIMP-2protein expression in prostatic carcinoma was negative correlated with above features (P<0.05);(3) There was a negative correlation between MMP-2and TIMP-2expression in benign and malignant prostatic lesions (P<0.05).Conclusion:(1) This study suggests that MMP-2protein is positive expression in prostate tissue, while expression intensity level becomes higher and higher among three groups (BPH,PIN,PC), showing significant difference between any two groups (P<0.05);(2) TIMP-2protein’s expression intensity level becomes higher and higher among three groups, showing significant difference between any two groups (P<0.05);(3) MMP-2protein expression in prostatic carcinoma was positive correlated with tumor stage, and histological grade(P<0.05), while TIMP-2protein expression was negatively correlated with the above features(P<0.05);(4) There was a negative correlation between MMP-2and TIMP-2expression(P<0.001) in prostatic lesions. MMP-2may have cooperation with TIMP-2in the process of molecular regulation of PC via synergistic actions, preventing the occurrence and development of prostate cancer. Low TIMP-2protein expression and elevated activation of MMP-2are involved in the malignant transformation of prostatic epithelium and may play a great role in the genesis and development of prostatic tumor.