妊娠相关乳腺癌金属蛋白酶1组织抑制剂和纤维连接蛋白1的表达及其与E-钙黏蛋白表达和预后的相关性  

Correlations of expressions of tissue inhibitor of matrix metalloproteinase-1 and fibronectin 1 in pregnancy associated breast cancer with expression of E-cadherin and prognosis

作　　者：靳继海[1] 蔺广荣 刘玉娟[3] 付丽梅[4] Jin Jihai;Lin Guangrong;Liu Yujuan;Fu Limei(Department of Breast Surgery,Binzhou People's Hospital Affiliated to Shandong First Medical University,Binzhou 256610,China;Department of Thyroid Surgery,Binzhou People's Hospital Affiliated to Shandong First Medical University,Binzhou 256610,China;Department of Pediatrics,Binzhou People's Hospital Affiliated to Shandong First Medical University,Binzhou 256610,China;Department of Pathology,Binzhou People's Hospital Affiliated to Shandong First Medical University,Binzhou 256610,China)

机构地区：[1]山东第一医科大学附属滨州市人民医院乳腺外科,滨州256610 [2]山东第一医科大学附属滨州市人民医院甲状腺外科,滨州256610 [3]山东第一医科大学附属滨州市人民医院儿科,滨州256610 [4]山东第一医科大学附属滨州市人民医院病理科,滨州256610

出　　处：《肿瘤研究与临床》2023年第3期179-184,共6页Cancer Research and Clinic

基　　金：山东省医药卫生科技发展计划(202004011168)。

摘　　要：目的探讨金属蛋白酶1组织抑制剂(TIMP1)和纤维连接蛋白1(FN1)在妊娠相关乳腺癌(PABC)中的表达及其与E-钙黏蛋白(E-cad)表达的相关性。方法回顾性收集2011年1月至2020年12月山东第一医科大学附属滨州市人民医院55例PABC患者临床病理资料。采用免疫组织化学法检测留存的石蜡包埋癌组织及对应癌旁组织(距离癌灶边缘>3 cm)中TIMP1、FN1及E-cad的表达;应用蛋白质印迹法检测其中10例PABC患者术中冻存的新鲜癌组织及癌旁组织中TIMP1和FN1蛋白的表达。采用χ^(2)检验分析TIMP1和FN1表达与患者临床病理特征的关系,采用Spearman法分析二者与E-cad表达的相关性,采用Kaplan-Meier法分析二者表达与生存间的关系。结果TIMP1、FN1在PABC组织中的阳性率分别为72.7%(40/55)、58.2%(32/55),在癌旁组织中的阳性率分别为25.5%(14/55)、18.2%(10/55),差异均有统计学意义(χ^(2)值分别为24.59、18.64,均P<0.001)。蛋白质印迹法检测结果显示,10例PABC患者新鲜癌组织中TIMP1和FN1蛋白的相对表达量均高于其对应的癌旁组织(1.60±0.76比0.62±0.29,1.31±0.62比0.44±0.15),差异均有统计学意义(t值分别为5.92、4.86,均P<0.001)。PABC中TIMP1、FN1的表达与雌激素受体表达、Ki-67阳性指数、TNM分期及淋巴结转移均有关(均P<0.05)。PABC中TIMP1、FN1表达与E-cad表达均呈负相关(r值分别为-0.471、-0.432,均P<0.001)。5例失访,其余50例中位随访43个月(12~90个月),50例中TMP1阳性36例,FN1阳性29例。TIMP1、FN1阴性组总生存均优于对应的阳性组(χ^(2)值分别为4.49、6.06,均P<0.05),其中,TIMP1、FN1阳性组中位总生存时间分别为51个月(95%CI 37~65个月)、43个月(95%CI 32~53个月),阴性组分别为89个月(95%CI 84~93个月)、87个月(95%CI 85~92个月)。结论PABC组织中TIMP1、FN1表达均升高,均与E-cad表达负相关,TIMP1、FN1可能通过上皮间质转化参与PABC的侵袭,且影响患者预后。Objective To investigate the expressions of tissue inhibitor of matrix metalloproteinase-1(TIMP1)and fibronectin 1(FN1)in pregnancy associated breast cancer(PABC)and their correlations with expression of E-cadherin(E-cad).Methods The clinicopathological data of 55 PABC patients in Binzhou People's Hospital Affiliated to Shandong First Medical University from January 2011 to December 2020 were retrospectively analyzed.Immunohistochemistry was used to detect expressions of TIMP1,FN1 and E-cad in cancer tissues and corresponding paracancerous tissues(>3 cm from the edge of the tumor foci).The expressions of TIMP1 and FN1 proteins in fresh intraoperative frozen cancer tissues and paracancerous tissues of 10 PABC patients were detected by Western blotting.The correlations of TIMP1 and FN1 expressions with clinicopathological characteristics of patients were analyzed byχ^(2) test,the correlation of TIMP1 and FN1 expressions with E-cad expression was analyzed by Spearman method,and the correlation of TIMP1 and FN1 expressions with survival was analyzed by Kaplan-Meier method.Results The positive rates of TIMP1 and FN1 in PABC tissues were 72.7%(40/55)and 58.2%(32/55),and 25.5%(14/55)and 18.2%(10/55)in paracancerous tissues,and the differences were statistically significant(χ^(2) values were 24.59 and 18.64,both P<0.001).The results of Western blotting showed that the relative expressions of TIMP1 and FN1 proteins in the fresh cancer tissues of 10 PABC patients was higher than those in the corresponding paracancerous tissues(1.60±0.76 vs.0.62±0.29,1.31±0.62 vs.0.44±0.15),and the differences were statistically significant(t values were 5.92 and 4.86,both P<0.001).The expressions of TIMP1 and FN1 in PABC tissues were correlated with estrogen receptor expression,Ki-67 positivity index,TNM stage and lymph node metastasis(all P<0.05).The expressions of TIMP1 and FN1 were negatively correlated with expression of E-cad in PABC(r values were-0.471 and-0.432,both P<0.001).Five cases were lost to follow-up,and the remaining

关 键 词：乳腺肿瘤 癌 妊娠相关 金属蛋白酶1组织抑制剂 纤连蛋白类 钙黏着糖蛋白类 上皮细胞-间质细胞转换 预后 

分 类 号：R737.9[医药卫生—肿瘤] R714.2[医药卫生—临床医学]