MMP—9、CDK8和VEGF—C的表達與宮頸癌臨床病理特點的關系

王海清　胡杏軍　劉芳

【摘要】 目的 探討基質金屬蛋白酶9（MMP-9）、細胞周期蛋白依賴性蛋白激酶8（CDK8）和血管內皮生長因子C（VEGF-C）在宮頸癌組織中的表達及臨床意義。方法 應用二步法免疫組織化學染色對70例宮頸癌組織進行MMP-9、CDK8及VEGF-C蛋白檢測， 觀察三者表達情況及其表達與臨床病理特征的關系， 并分析宮頸癌組織MMP-9表達與CDK8、VEGF-C表達的關系。結果 MMP-9、CDK8、VEGF-C在臨床分期Ⅲ期的陽性表達高于Ⅱ期， 有淋巴轉移者的陽性表達高于無淋巴轉移者， 宮頸浸潤深度≥2/3者的陽性表達高于深度<2/3者， 組織分化低的陽性表達高于高、中分化， 差異均具有統計學意義（P<0.05）。宮頸癌組織中MMP-9與CDK8表達呈正相關（rs=0.518， P<0.05）， MMP-9與VEGF-C表達呈正相關（rs=0.657， P<0.05）。結論 MMP-9、CDK8和VEGF-C的過表達促進宮頸癌的浸潤轉移， 具有正協同作用。聯合檢測MMP-9、CDK8和VEGF-C蛋白可作為預測宮頸癌的浸潤轉移及評價患者預后的生物學指標。

【關鍵詞】 宮頸癌；基質金屬蛋白酶9；細胞周期蛋白依賴性蛋白激酶8；血管內皮生長因子C；免疫組織化學

DOI：10.14163/j.cnki.11-5547/r.2017.25.004

【Abstract】 Objective To investigate the expression of matrix metalloproteinase-9 （MMP-9）， cyclin-dependent kinases-8 （CDK8） and vascular endothelial growth factor-C （VEGF-C） in cervical cancer tissue and its clinical significance. Methods The expression of MMP-9， CDK8 and VEGF-C in 70 cases of cervical cancer was detected by two-step immunohistochemical staining. The relationship between the expression of MMP-9， CDK8 and VEGF-C was observed and the expression of MMP-9 was analyzed. CDK8， VEGF-C expression. Observation were made on expressio of the above three proteins and its correlation with clinicopathological features， and analysis was made on correlation between the expression of MMP-9 and the expression of CDK8 and VEGF-C in cervical cancer. Results MMP-9， CDK8， VEGF-C positive expression in clinical stage Ⅲ was higher than that in stage Ⅱ， the positive expression lymphatic metastasis was higher than those without lymph node metastasis， the positive expression of infiltration depth ≥2/3 was higher than those of the cervical depth <2/3， and the positive expression of low tissue differentiation was higher than that of middle-high differentiation. Their difference had statistical significance （P<0.05）. The expression of MMP-9 was positively correlated with the expression of CDK8 in cervical cancer （rs=0.518， P<0.05）， and the expression of MMP-9 was positively correlated with VEGF-C （rs=0.657， P<0.05）. Conclusion The overexpression of MMP-9， CDK8 and VEGF-C promotes the invasion and metastasis of cervical cancer and it has synergistic effect. Combined detection of MMP-9， CDK8 and VEGF-C proteins can be used as a biological marker to predict the invasion and metastasis of cervical cancer and evaluate the prognosis of cervical cancer.

【Key words】 Cervical cancer； Matrix metalloproteinase-9； Cyclin-dependent kinases-8； Vascular endothelial growth factor-C； Immunohistochemistryendprint

癌細胞的浸潤和轉移是宮頸癌的晚期死亡原因之一。基質金屬蛋白酶（matrix metalloproteinase， MMP）家族中的MMP-9有助于腫瘤的侵襲和轉移[1]。腫瘤的發生、發展， 須有2個或以上的功能不同癌基因同時被激活， 并且在時空上相互配合[2]。本研究應用二步法免疫組織化學染色從蛋白水平聯合檢測MMP-9、CDK8及VEGF-C在宮頸癌組織中的表達， 并探討其與臨床病理學特征的相關性， 為宮頸癌的早診斷、早治療和預后判斷提供實驗依據。

1 材料與方法

1. 1 材料 收集2011年1月～2016年5月中山大學附屬江門醫院病理科存檔的宮頸浸潤鱗癌標本70例：無淋巴結轉移31例， 伴淋巴結轉移39例；病理組織學分級：Ⅰ級20例， Ⅱ級26例， Ⅲ級24例。腫瘤臨床分期（FIGO， 2000年）：Ⅱ期

27例， Ⅲ期43例。患者年齡21～77歲， 平均年齡49.1歲。所有病例標本取檢前均未行放療和化療。每例標本經病理學檢查證實， 有詳細的臨床資料和手術記錄。

1. 2 方法……