膀胱癌中nm23-H1基质金属蛋白酶及其抑制物的表达及其临床意义

目的nm23-H1是抑制肿瘤转移的代表性基因,在人类乳腺癌、肝癌、胃癌、卵巢癌、恶性黑色素瘤等肿瘤的研究中均发现nm23-H1表达下降或不表达与肿瘤的转移过程以及不良预后密切相关;基质金属蛋白酶-2(MMP-2)及其抑制物(TIMP-2)调控着细胞外基质的降解,在肿瘤浸润、转移过程中发挥重要作用。因此,探讨膀胱癌组织中nm23-H1、MMP-2与TIMP-2的蛋白表达及其与临床、病理指标之间的关系具有非常重要的意义。方法采用免疫组织化学SP法分析69例手术切除膀胱癌中nm23与MMP-2、TIMP-2蛋白的表达情况。结果nm23-H1、MMP-2在正常膀胱黏膜与膀胱移行细胞癌(TCCB)中的表达差异有统计学意义(P<0.01),其中nm23-H1表达与肿瘤病理分级、临床分期以及是否转移呈负相关,MMP-2蛋白表达与肿瘤分级、分期呈正相关;在肿瘤组织中随TCCB临床病理分期升高nm23-H1的表达呈现降低趋势,而MMP-2表达随TCCB临床病理分期升高呈现增高趋势,且差异有统计学意义(P<0.05)。此外,MMP-2在≥2 cm的肿瘤中有较高的表达率,且差异有统计学意义(P<0.05)。TIMP-2在TCCB中的表达随病理分级、临床分期的增高而降低,但差异无统计学意义(P>0.05)。结论检测膀胱癌转移相关基因表达并分析其表达的相互关系,有助于判断膀胱癌的转移潜能及指导术后干预治疗。

Clinical significance of expression of nm23-H1,MMP-2 and TIMP-2 in bladder carcinoma

Objective To investigate the reationship of the expressions of nm23-H1,MMP-2 and TIMP-2 in bladder carcinoma and thier clinical significane.Methods Immunohistochemical study on nm23-H1,MMP-2 and Timp-2 were performed on 69 samples of bladder transitional cell carcinoma of paraffin-embedded specimens of surgical carcinoma.Results There was significant difference in nm23-H1 and MMP-2 between bladder transitional cell carcinoma and normal bladder epithelium(P<0.01).The positive expression of nm23-H1 was decreased with the staging,grading and metastasis(P<0.05).But the positive expression of MMP-2 was significantly increased with staging and grading(P<0.05).Furthermore,the positive rate of MMP-2 was increased in tumor diameter greater than 2 cm,which showed statistical significance(P<0.05).The positive expression of TIMP-2 was decreased with the staging and grading and the expression intensity of TIMP-2 was increased with staging and grading,but their was not showed statistical significance.Conclusion The expression of some metastasis-related genes can be used to estimite the metastatic potenciality and help for the adjuvant treatment.