凝血酶受体-1在肺癌组织中的表达及其与转移的关系

目的研究凝血酶受体（PAR）-1在肺癌组织中的表达及其与肺癌侵袭、转移的关系。方法免疫组织化学sP法、形态学计量及逆转录-聚合酶链反应（RT-PCR）检测肺癌原发灶和转移灶组织（36例液氮冻存肺癌组织、80例石蜡包埋肺癌组织）中PAR-1的表达。结果具有侵袭和转移部位的癌巢、脉管内癌栓、癌周围的肺泡上皮不典型增生灶及支气管腺导管上皮不典型增生灶均呈现较强的阳性反应。肺癌组织PAR-1蛋白表达阳性率为73．8％（59／80例）;转移组85．7％（48／56）与非转移组45,8％（11／24）之间差异有统计学意义（P〈0．05）。转移和非转移（P〈0．05）、原发灶和转移灶（P〈0．05）、肿瘤组织和肺组织（P〈0．01）各组之间PAR．1蛋白含量差异有统计学意义;而肿瘤大小、组织学类型和组织学分化各组间差异无统计学意义（P〉0．05）。肺癌组织PAR．1mRNA表达阳性率63．9％（23／36例）;转移组78．3％（18／23例）与非转移组38．5％（5／13）之间差异有统计学意义（P〈0．05）。结论PAR-1过度表达与肺癌的转移表型、组织发生及恶性表型有关;PAR-1可能是肺癌转移过程中发挥重要作用的因素之一。

Expression of PAR-1 in human lung carcinoma and its relationship with tumor metastatic potential

Objective To explore the correlation between expression of PAR-1 and metastasis of human lung carcinoma.Methods Expression levels of PAR-1 were examined in surgically resected lung carcinoma specimens and corresponding lymph nodes by RT-PCR and immunohistochemistry,combined with morphometric methodology and clinicopathologic profiles.Results Strong PAR-1 staining was detected in the periphery of carcinoma nests,adenocarcinomatous emboli,foci of atypical adenomatous hyperplasia adjacent to the adenocarcinoma and atypical proliferation of duct epithelium of bronchial mucous glands.The expression rates of PAR-1 were 73.8%(59/80) and 63.9%(23/36) by immunohistochemistry and RT-PCR respectively.The percentage of PAR-1 protein expression cells was significantly higher in tumors with metastasis(85.7%,48/56) than those without(45.8%,11/24).Morphometric study demonstrated that there were significant differences of PAR-1 protein expression levels between tumors with metastatic and those without,primary and metastatic carcinomas,primary carcinomas and benign lung tissues adjacent to the carcinoma.No significant correlation was found between PAR-1 expression level and tumor size,histological types and tumor grades.The positive rate of PAR-1 mRNA expression in the metastatic group was significantly higher than that of the non-metastatic group(78.3%,18/23 v.s.38.5%,5/13).Conclusion PAR-1 expression may play an important role in determing the malignant phenotypes of lung cancers and significantly contribute to their initiation,progression and metastasis.