Abstract
BackgroundDiscordant results exist about the role of human epidermal growth factor receptor 2 (HER2) overexpression and/or HER2 amplification in lung adenocarcinoma. We aimed to compare the performance of HercepTest and PATHWAY anti-HER2 (4B5) by correlating immunohistochemistry (IHC) results with silver in situ hybridization (SISH) in adenocarcinoma lung specimens.MethodsA total of 148 surgically resected adenocarcinoma lung specimens were included.ResultsHER2 overexpression was found in 7.4% patients for HercepTest Dako and in 2.7% patients for 4B5 antibody. The overall coincidence between these two types of antibodies equals 93.9%. The incidence of HER2 amplification in lung adenocarcinoma was 17.6%, of which in 2.7% of the cases high-grade amplification was present. HER2 amplification was present in 90.9% of patients with overexpression of HER2, obtained by using HercepTest Dako and 75% patients using 4B5 antibody. A significant correlation between overexpression of HER2 receptors obtained by HercepTest Dako and 4B5 antibody and HER2 amplification was shown.ConclusionThe research of the efficiency of targeted molecular therapies with an HER2 antibody may serve as a basis for the introduction of routine HER2 status determination in lung adenocarcinoma, dictating the need for the standardized protocol for HER2 status determination in such pathology.
Highlights
Lung cancer is a heterogeneous disease and mutation profiling has become a routine practice in pulmonary oncology [1]
By testing the coincidence between the results of Human epidermal growth factor receptor 2 (HER2) overexpression obtained by applying HercepTest (Dako) antibodies and the results obtained by applying PATHWAY anti-HER2 (4B5) antibodies, coincidence was established in three cases (2% of the total samples)
Our study is the first study to use the same samples of lung adenocarcinoma tumour tissue for the IHC determination of HER2 expression by applying two different antibodies (Hercep Test Dako and Ventana anti-HER2/neu (4B5))
Summary
Lung cancer is a heterogeneous disease and mutation profiling has become a routine practice in pulmonary oncology [1]. The Lung Cancer Mutation Consortium was established in 2008 as a multinational programme investigating the frequency of selected oncogenic mutations in lung adenocarcinoma and using the obtained results for the application of targeted therapies. Oncogenes were detected in 64% of lung adenocarcinomas [2], while available information in relation to EGFR, BRAF, KRAS, ALK, ROS1, and MET gene mutations in lung adenocarcinomas are growing steadily. Among the proto-oncogene products, the epidermal growth factor (EGF) receptor family plays an important role in local tumour growth. Human epidermal growth factor receptor 2 (HER2) protein overexpression and/or HER2 gene amplification has a key role in the development and progressing of many carcinomas, especially breast and stomach cancer [3,4], and in non-small cell lung carcinoma (NSCLC) [5,6]. The frequency of HER2 overexpression and HER2 gene amplification in NSCLC varies significantly from one study to another, but the majority of authors agree that overexpression and amplification are most prevalent in adenocarcinomas as compared to other histological types
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