Significant relationship of matrix metalloproteinase 9 with nuclear grade and prognostic impact of tissue inhibitor of metalloproteinase 2 for incidental clear cell renal cell carcinoma
Significant relationship of matrix metalloproteinase 9 with nuclear grade and prognostic impact of tissue inhibitor of metalloproteinase 2 for incidental clear cell renal cell carcinoma
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DOI：
10.1016/j.urology.2007.02.044
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发表时间：
2007-06-01
期刊：
影响因子：
2.1
通讯作者：
Takahashi, Satoru
中科院分区：
文献类型：
--
作者：
Kawata, Nozomu;Nagane, Yusuke;Takahashi, Satoru
目的观察肿瘤对基质金属蛋白酶2和9 （MMP-2、MMP-9）、组织金属蛋白酶1和2抑制剂（TIMP-1、TIMP-2）、膜型金属蛋白酶1 （MT-MMP-1）的免疫反应性，探讨偶发性肾细胞癌的最佳评价方法。方法对120例偶然透明细胞肾细胞癌（ICRCC）患者的肿瘤标本进行手术采集，均无远处转移或侵犯Gerota筋膜外。免疫组织化学染色检测MMP-2、MMP-9、TIMP-1、TIMP-2和MT-MMP-1。这些因素的免疫反应性通过半定量多变量分析来分析癌症特异性生存。结果肿瘤特异性5年和10年生存率分别为91.4%和91.4%。单因素分析显示，核分级（P = 0.0064）和TIMP-2 （P = 0.034）是预后的重要因素。基质金属蛋白酶9与高核级RCC有显著相关性（P = 0.017）， COX多元回归分析发现基质金属蛋白酶9是一个独立的预测因子（P = 0.0028）。结论核分级和TIMP-2是影响ICRCC预后的重要因素。多变量分析显示，大于3级的核分级与癌症死亡几率显著增加566%相关。强表达MMP-9与高核分级几率增加774%相关，差异有统计学意义。尽管众所周知ICRCC预后良好，但对于核分级高且MMP-9和TIMP-2表达强烈的肿瘤患者，应进行严格的术后随访。
Objective To examine the immunoreactivity of tumors for matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1, TIMP-2), and membrane type MMP 1 (MT-MMP-1), to evaluate the Optimum assessment of incidental renal cell carcinoma.Methods Tumor samples from 120 incidental clear cell renal cell carcinoma (ICRCC) patients without distant metastasis or invasion beyond Gerota's fascia were obtained by surgery. They were immunohistochemically stained for MMP-2, MMP-9, TIMP-1, TIMP-2, and MT-MMP-1. Immunoreactivity for these factors was analyzed by semiquantitative multivariate analysis for cancer-specific Survival.Results The cancer-specific 5 and 10-year survival rates were 91.4% and 91.4%, respectively. Univariate analysis revealed that nuclear grade (P = 0.0064) and TIMP-2 (P = 0.034) were significant prognostic factors. Matrix metalloproteinase 9 has a significant relationship with high nuclear grade RCC (P = 0.017) and Was found to be an independent prognosticator by COX multiple regression analysis (P = 0.0028).Conclusions Nuclear grade and TIMP-2 were significant prognostic factors of ICRCC. Multivariate analysis showed that a nuclear grade greater than 3 was associated with a 566% significant increase in the odds of cancer death. Strong expression of MMP-9 was associated with a 774% increase in the odds of high nuclear grade, with statistical significance. Although ICRCC is well known for having a favorable prognosis, patients with tumors having a high nuclear grade and strongly expressed MMP-9 and TIMP-2 should undergo strict postoperative follow-up.