MMP_2、MMP_9、TIMP_1、TIMP_2和CD44V6在非小细胞肺癌中的表达及与转移、预后的关系

Expression and metastasis prognosis of CD44V6 MMP_2,MMP_9,TIMP_1 and TIMP_2 in non-small cell lung cancer

目的探讨CD44V6、基质金属蛋白酶MMP2、MMP9及抑制剂TIMP1、TIMP2在非小细胞性肺癌(NSCLC)中的表达及与转移、预后的关系。方法采用免疫组织化学S-P法,分别检测43例NSCLC组织、15例正常支气管上皮组织中CD44V6、MMP2、MMP9、TIMP1及TIMP2的蛋白表达。43例均随访或追观3年以上。结果43例NSCLC的CD44V6阳性表达率65.1%(28/43),15正常支气管上皮组织阳性表达13.3%(2/43),两者相比差异有显著性(P<0.05);肺鳞癌组织的CD44V6阳性率85.7%(18/21),肺腺癌组织阳性度45.5%(10/23),两者相比差异有显著性(P<0.01);Ⅲ期和Ⅰ期之间CD44V6表达有显著差异(P<0.05);肺癌伴淋巴结转移者的CD44V6表达高于未发生淋巴结转移者(P<0.05);CD44V6高表与患者3年生存期成负相关(P<0.05),但与肺癌细胞分化程度及临床参数等均无明显关系(P<0.05)。MMP2、MMP9、TIMP1及TIMP2在NSCLC中的阳性表达率(分别为79.1%、74.4%、55.8%及60.5%)明显高于正常支气管上皮组织(分别为27.7%、26.7%、20.0%、及26.7%)(P<0.01或P<0.05);腺癌中MMP9的阳性表达率(90.9%)显著高于鳞癌(57.1%,P<0.05);MMP2、MMP9的表达随着病理分级和临床分期增加而有增高趋势;而TIMPl、TIMP2的阳性表达则呈下降趋势。MMP2、MMP9、TIMP1及TIMP2的阳性表达率与患者淋巴结转移和3年生存期密切相关(P<0.05),但与患者的临床参数均无明显关系(P>0.05)。结论CD44V6、MMP2、MMP9、TIMPl及TIMP2的过度表达与NSCLC的发展、淋巴结转移及预后有密切关系,可作为临床评估NSCLC的进展及预测其转移潜能和预后的重要指标之一。

[Objective] To study the expression and metastasis, prognosis of CD44V6, MMP2, MMP9, TIMP1 and TIMP2 in non-small cell lung cancer （NSCLC）. [Methods] Immunohistochemical S-P method was used to detect the expression of CD44V6, MMP2, MMP9, TIMP1 and TIMP2 in 43 patients with NSCLC and 15 normal epithelial tissues of the lung. 43 patients with NSCLC were in long-term follow-up. [Results] The positive expression rate of CD44V6 in NSCLC （65.1%） was significantly higher than that in normal epithelial tissues of the lung. The positive rate of CD44V6 in squamous cell carcinoma was significantly higher than that in adenocarcinoma （P 〈0.01）, and much higher in stage Ⅲ than that in stage Ⅰ ＋ Ⅱ stages （P 〈0.01）. NSCLC with lymph node metastasis showed higher expression of CI）44V6, compared with that without lymph node metastasis （P 〈0.05）. The 3-year survival rate in pa-tients with low CD44V6 expression was significantly higher than that with high CD44V6 expression （P 〈0.05 ） respectively, while the expression of CD44V6 did not relate to tumor differentiation and chnical parameter （P 〉0.05）. The positive rates of MMP2, MMP9, TIMP1 and TIMP2 in NSCLC （79.1%, 74.4%, 55.8% and 60.5%） were much higher than those in normal epithehal tissues of the lung （P 〈0.05 or P 〈0.01）. The positive rates of MMP2, MMP9 were significantly higher in grade 3, stage Ⅲ than those in grade 1, stage Ⅰ or stage Ⅰ＋Ⅱ stages （P 〈0.05, P 〈0.01）. The positive rates of TIMP1, TIMP2 were much lower in grade 3, stage Ⅲ than those in grade Ⅰ, stage I or stage Ⅰ＋Ⅱ stages （P 〈0.05）. The expressions of MMP2, MMP9, TIMP1 and TIMP2 were closely associated with lymph node metastasis and 3-year survival rate of NSCLC （P 〈0.05） , but not with chnical parameter （P 〉0.05）. [Conclusions] Over expression of CD44V6, MMP2, MMP9, TIMP1 and TIMP2 may be closely correlated to the progression, metastasis and prognosis of the patients with NSCLC. It might be helpful to evaluate the progression of the cancer, and to predict the metastasis and prognosis of NSCLC.