膀胱癌中MMP-2及TIMP-2的表达与病理分期和预后的相关性

Correlation between expression of MMP-2 and TIMP-2 in human BTCC and pathologic grade, clinical stage and prognosis

目的探讨金属蛋白酶2(MMP-2)及其抑制因子(TIMP-2)在膀胱癌组织中的表达与病理学分级、分期和患者预后的相关性。方法采用免疫组化SP法,检测MMP-2及TIMP-2在40例膀胱癌和癌旁组织中的表达;术后随访2年。结果膀胱移行细胞癌(BTCC)组织中MMP-2表达阳性率为42.5%(17/40);TIMP-2表达阳性率为32.5%(13/40)。癌旁组织中MMP-2表达阳性率为25%(10/40),TIMP-2表达阳性率为20%(8/40)。对32例膀胱部分切除术患者随访2年,结果 12例膀胱癌复发。复发12例中,BTCC组织MMP-2表达阳率为91.6%(11/12),TIMP-2表达阳性率为33.3%(4/12);癌旁组织MMP-2表达阳率为66.7%(8/12),TIMP-2表达阳性率为16.7%(2/12)。结论 MMP-2和TIMP-2的表达阳性率BTCC显著高于癌旁组织(P<0.01)。BTCC组织中MMP-2的阳性表达与临床分级呈正相关(P<0.01);TIMP-2的阳性表达与临床分级相关不显著(P>0.05)。膀胱部分切除术患者高MMP-2阳性表达率和/或低TIMP-2阳性表达率以及癌旁组织MMP-2阳性表达与术后膀胱癌复发密切相关。高MMP-2阳性表达率和/或低TIMP-2阳性表达率表示膀胱癌浸润及转移能力增强;癌旁组织MMP-2阳性表达的膀胱癌具有恶性程度高、易复发的特点;提示手术时尽可能保证足够的切除范围。

Objective To investigate the expression of matrix metalloproteinases-2 （MMP-2） and tissue inhibitors of metalloproteinases-2（TIMP-2） in bladder transitional cell carcinoma（BTCC） and peritumoral tissue, and to explore their correlation with pathologic grade, stage of the tumors and prognosis. Methods SP method of immunohistochemistry was used to detect MMP-2 and TIMP-2 expression in 40 cases of BTCC, peritumoral tissue and 10 normal bladder tissues. Of the 40cases of BTCC, II were at G1, 13 at G2 and 16 at G3 according to pathologic grading; and 22cases were at Tis-T1, 18 at T2-T3 according to pathologic staging. Of the 40 cases of BTCC, 32 were taken partial cystectomy and 8 taken radical cystectomy. Results MMP-2 and TIMP-2 expression were uniformly negative in all of normal bladder tissues. The expression of MMP-2 and TIMP-2 in BTCC was 42.5%（17/40） and 32.5%（13/40） respectively. The expression of MMP-2 and TIMP-2 in peritumoral tissue was 25%（10/40） and 20%（8/40） respectively. The expression of MMP-2 and TIMP-2 in BTCC was 18.2%（2/ 11） and 27.3%（3/11） at G1 respectively, was 38.5%（5/13） and 38.5%（5/13） at G2 respectively, was 62.5%（10/16） and 31.3%（5/16） at G3 respectively, was 31.8%（7/22） and 40.9%（9/22） at Tis-T1 respectively, was 55.6%（10/18） and 22.2%（4/18） at T2-T3 respectively. The expression of MMP-2 and TIMP-2 in peritumoral tissue was 0%（0/11） and 0%（1/11） at G1 respectively, was 23.1%（3/13） and 15.4%（2/13） at G2 respectively, was 43.8%（7/16） and 31.3%（5/16） at G3 respectively, was 13.6%（3/22） and 22.7%（5/22） at Tis-T1 respectively, was 38.9%（7/18） and 16.7%（3/18） at T2-T3 respectively. The MMP-2 and TIMP-2 positive rate was significantly correlated with the tumor grade and stage （P〈0.01）, MMP-2 and TIMP-2 positive rate was different in superficial and invasive bladder cancer （P〈0.05）. The high expression of MMP-2 and MMP-2/TIMP-2 was positively correlated with the carcinoma relapse. Conclusion MMP-2 and TIMP-2 expression is positively correlated with the grade and stage of bladder cancer, indicating that expression increase of MMP-2 protein in BTCC is associated with poor prognosis outcome of BTCC. MMP-2 positive in bladder cancer show high malignant and easily relapse. By contrast, the abnormal expression of TIMP-2 and its function of inhibiting tumor infiltration and migration need further investigation. MMP2 can be used as a useful molecular marker for prognosis of BTCC. The MMP-2 positive expression of peritumoral tissue was higher in invasive bladder cancer than superficial bladder. In order to get a good prognosis, operation must be tried the best to enlarge partial cystectomy for the malignance area or radical cystectomy.