肺癌组织学亚型中不同的紧密连接蛋白表达谱。

Distinct claudin expression profile in histologic subtypes of lung cancer.

作者信息

Moldvay Judit, Jäckel Márta, Páska Csilla, Soltész Ibolya, Schaff Zsuzsa, Kiss András

机构信息

Department of Pulmonology, Semmelweis University Budapest, Budapest, Diósárok u. 1/c. H-1125, Hungary.

出版信息

Lung Cancer. 2007 Aug;57(2):159-67. doi: 10.1016/j.lungcan.2007.02.018. Epub 2007 Apr 6.

DOI:10.1016/j.lungcan.2007.02.018

PMID:17418912

Abstract

PURPOSE

Claudins are the main constituents of tight junctions. Little is known about their expression and localization in the normal bronchial epithelium and in lung cancer.

PATIENTS AND METHODS

One hundred four lung cancer tissue blocks were studied including 46 adenocarcinomas (ADC), 30 squamous cell carcinomas (SCC), 15 small cell lung cancers (SCLC), 8 typical and 5 atypical carcinoids. All slides contained normal bronchial mucosa as well. Immunohistochemistry using antibodies against claudins-1, -2, -3, -4, and -7 proteins, as well as semi-quantitative estimation were performed. RT-PCR analysis was also carried out in 22 immunohistochemically representative tumor samples.

RESULTS

Normal bronchial epithelial cells expressed all the examined claudin proteins. When compared, SCLCs and carcinoids showed striking differences in regard to claudins-1, -3, and -4 expressions (p<0.0001, p<0.0001, and p<0.0004, respectively), whereas ADCs and SCCs revealed significant differences in claudins-3, -4, and -7 expressions (p<0.0001, p<0.0001, and p<0.0053, respectively). However, comparison of ADCs with SCLCs revealed significant difference only in claudin-2 expression (p<0.0002). The comparison of ADCs and carcinoids resulted in significant differences regarding claudins-1, -3, and -4 expressions (p<0.0006, p<0.0001, and p<0.0001, respectively). SCCs and SCLCs varied in respect to claudin-2, -3, and -4 expressions (p<0.0009, p<0.0001, and p<0.0019, respectively), whereas SCCs and carcinoids showed different claudins-1 and -4 expressions (p<0.0076 and p<0.0045, respectively). RT-PCR analysis revealed parallel changes in the mRNA and protein expression of certain claudins.

CONCLUSIONS

The observed distinct claudin expression profile within the non-small cell lung cancer group, further, the marked differences between SCLCs and carcinoids may have differential diagnostic impact, and the overexpression of certain claudins might have therapeutic implications.

摘要

目的

紧密连接蛋白是紧密连接的主要组成成分。关于它们在正常支气管上皮和肺癌中的表达及定位知之甚少。

患者与方法

研究了104个肺癌组织块，包括46例腺癌（ADC）、30例鳞状细胞癌（SCC）、15例小细胞肺癌（SCLC）、8例典型类癌和5例非典型类癌。所有切片也均包含正常支气管黏膜。采用针对紧密连接蛋白-1、-2、-3、-4和-7蛋白的抗体进行免疫组织化学检测以及半定量评估。还对22个免疫组织化学代表性肿瘤样本进行了逆转录聚合酶链反应（RT-PCR）分析。

结果

正常支气管上皮细胞表达所有检测的紧密连接蛋白。相比之下，小细胞肺癌和类癌在紧密连接蛋白-1、-3和-4的表达方面存在显著差异（分别为p<0.0001、p<0.0001和p<0.0004），而腺癌和鳞状细胞癌在紧密连接蛋白-3、-4和-7的表达上有显著差异（分别为p<0.0001、p<0.0001和p<0.0053）。然而，腺癌与小细胞肺癌相比，仅在紧密连接蛋白-2的表达上有显著差异（p<0.0002）。腺癌与类癌的比较在紧密连接蛋白-1、-3和-4的表达上产生显著差异（分别为p<0.0006、p<0.0001和p<0.0001）。鳞状细胞癌和小细胞肺癌在紧密连接蛋白-2、-3和-4的表达上有所不同（分别为p<0.0009、p<0.0001和p<0.0019），而鳞状细胞癌和类癌在紧密连接蛋白-1和-4的表达上存在差异（分别为p<0.0076和p<0.0045）。RT-PCR分析显示某些紧密连接蛋白的mRNA和蛋白表达有平行变化。