Miyata Yasuyoshi, Kanda Shigeru, Nomata Koichiro, Hayashida Yasushi, Kanetake Hiroshi
Department of Urology, Nagasaki University School of Medicine, Nagasaki City, Nagasaki, Japan.
Urology. 2004 Mar;63(3):602-8. doi: 10.1016/j.urology.2003.09.035.
To investigate the relationship between the expression of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, and TIMP-2 and pT stage or survival in patients with transitional cell carcinoma of the upper urinary tract. MMP-2 and MMP-9 are associated with tumor invasion in several malignancies. TIMPs exert an anti-invasive effect by blocking MMP activity. Recent studies have shown, however, that TIMPs can also stimulate cell proliferation and angiogenesis.
Tumor sections surgically removed from 91 patients were examined for expression of MMP-2, MMP-9, TIMP-1, and TIMP-2 by immunohistochemistry. We also determined the proliferation index and microvessel density in each tumor and investigated the independent roles of these factors in tumor stage and survival using multivariate analysis.
Of 91 tissue samples, 50, 51, 45, and 39 were positive for MMP-2, MMP-9, TIMP-1, and TIMP-2 expression, respectively. Tumors positive for MMP-2, MMP-9, and TIMP-1 exhibited a greater proliferation index than tumors with negative expression (P <0.001, P = 0.013, and P <0.001, respectively). The microvessel density of tumors positive for MMP-2 and TIMP-1 was greater than that of negative tumors (P <0.001). The expression of MMP-2, MMP-9, and TIMP-1 was an independent predictor of high pT stage. Cox proportional hazard analysis identified TIMP-1 expression as an independent factor for cause-specific survival (odds ratio 5.2, P = 0.011), similar to microvessel density, pT4, and lymph node metastasis.
TIMP-1 expression correlated with pT stage and was an independent predictor of cause-specific survival. Our results suggest that TIMP-1 expression is a potentially useful tool for the selection of postoperative observation strategies in patients with transitional cell carcinoma of the upper urinary tract.
探讨基质金属蛋白酶（MMP）-2、MMP-9、金属蛋白酶组织抑制剂（TIMP）-1和TIMP-2的表达与上尿路移行细胞癌患者的pT分期或生存率之间的关系。MMP-2和MMP-9在多种恶性肿瘤中与肿瘤侵袭相关。TIMP通过阻断MMP活性发挥抗侵袭作用。然而，最近的研究表明，TIMP也可刺激细胞增殖和血管生成。
对手术切除的91例患者的肿瘤切片进行免疫组织化学检查，以检测MMP-2、MMP-9、TIMP-1和TIMP-2的表达。我们还测定了每个肿瘤的增殖指数和微血管密度，并使用多变量分析研究了这些因素在肿瘤分期和生存中的独立作用。
在91份组织样本中，MMP-2、MMP-9、TIMP-1和TIMP-2表达阳性的分别有50、51、45和39份。MMP-2、MMP-9和TIMP-1表达阳性的肿瘤比表达阴性的肿瘤表现出更高的增殖指数（分别为P<0.001、P=0.013和P<0.001）。MMP-2和TIMP-1表达阳性的肿瘤微血管密度大于阴性肿瘤（P<0.001）。MMP-2、MMP-9和TIMP-1的表达是高pT分期的独立预测指标。Cox比例风险分析确定TIMP-1表达是特定病因生存率的独立因素（比值比5.2，P=0.011），类似于微血管密度、pT4和淋巴结转移。
TIMP-1表达与pT分期相关，是特定病因生存率的独立预测指标。我们的结果表明，TIMP-1表达是上尿路移行细胞癌患者术后观察策略选择的一个潜在有用工具。
