非小细胞肺癌EGFR和HER2基因状态及相关性

EGFR and HER2 gene expression status and their correlation in non-small cell lung cancer

目的探讨EGFR和HER2基因变化在非小细胞肺癌发生发展中的作用及其二者相关性。方法采用PathVysionTM探针试剂盒和LSI EGFR SpectrumOrange／CEP7 SpectrumGreen探针组合,对31例中国人非小细胞肺癌石蜡切片标本,其中腺癌20例、鳞癌2例、大细胞癌2例、细支气管肺泡癌4例、腺鳞癌3例,分别进行EGFR和HER2基因状态的检测,并统计分析二者之间的相关性。结果EGFR基因扩增者6例;EGFR基因无扩增的25例中4例为四体,5例为多体,EGFR基因拷贝数增加和基因扩增者共15例(15／31)。HER2基因扩增者2例;HER2基因无扩增的29例中4例为三体,1例为四体,9例为多体,HER2基因拷贝数增加和基因扩增者共16例(16／31)。同时为EGFR和HER2基因异常(包括基因扩增和拷贝数增高)者12例(12／31),而且几乎都是临床Ⅲ期至Ⅳ期的患者。EGFR和HER2基因异常之间的相关性X2Adj=7．3045,P确切=0．0069。结论EGFR或HER2基因扩增在非小细胞肺癌中的发生率较低,但基因拷贝数增加是较常发生的事件。EGFR和HER2异常有相关性,EGFR和HER2基因都参与了非小细胞肺癌的发生发展,EGFR和HER2二聚体是肺癌常见的异源二聚体形式,而且它们的相互作用可能与疾病进展有关。

Objective To explore epidermal growth factor receptor （EGFR） and HER2 gene status, to assess the correlation between EGFR and HER2 gene status, and to investigate the role of copy number increase and amplification of EGFR gene and HER2 gene in the tumorigenesis and disease progression of non-small-cell lung cancer. Methods Using PathVysion^TM kit and LSI EGFR SpectrumOrange/CEP7 SpectrumGreen probes, EGFR gene and HER2 gene status were evaluated by fluorescence insitu hybridization （FISH） using formalin-fixed, paraffin-embedded samples from 31 patients with non-small-cell lung cancer, including 20 adenocareinomas, 2 squamous cell carcinomas, 2 large cell carcinoma, 4 bronchoalveolar carcinomas and 3 adenosquamous carcinomas. The correlation between EGFR and HER2 gene status was analyzed. Results Six of thirty-one carcinomas showed EGFR gene amplification. Of 25 cases without EGFR gene non-amplification, four tetrasomy and 5 polysomy were detected. Overall, 15 out of 31 carcinomas demonstrated either EGFR gene copy number increase or gene amplification （15/31）. HER2 gene amplification was seen in 2 of the 31 cases. Four trisomy, one tetrasomy and nine polysomy cases were found in 29 tumors that had no HER2 gene amplification. Overall, 16 of 31 cases showed either HER2 gene copy number increase and/or amplification （16/31）. Synchronous EGFR and HER2 gene numerical changes, i.e. gene copy number increase and gene amplification, were found in 12 of 31 cases （12/31）, and almost all such patients had either clinical stage Ⅲ or Ⅳ tumor. EGFR gene numerical changes significantly correlated with HER2 gene abnormality （X^2Adj = 7.3045, P = 0.0069）. Conclusions EGFR or HER2 copy number increase is much more frequent than gene amplification in no-small-cell lung cancer. Our data based on gene alterations indicate, for the first time, that there is a significant correlation between EGFR alterations and HER2 abnormalities. Both genes are involved in the tumorigenesis and development of lung cancer. EGFR/HER2 dimer is one of the predominant heterodimerization types in lung cancer. The interactions between EGFR and HER2 may play a rule in the progression of non-small-cell lung cancer.