HER-2/neu alterations in non-small cell lung cancer: A comprehensive evaluation by real time reverse transcription-PCR, fluorescence in situ hybridization, and immunohistochemistry

• Published in: Clinical cancer research 2003-09, Vol.9 (10), p.3645-3652
• Main Authors: PELLEGRINI, Caterina, FALLENI, Monica, MARCHETTI, Antonio, CASSANI, Barbara, MIOZZO, Monica, BUTTITTA, Fiamma, RONCALLI, Massimo, COGGI, Guido, BOSARI, Silvano
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Female; Genes, erbB-2 - genetics; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Male; Medical sciences; Middle Aged; Pneumology; Receptor, ErbB-2 - biosynthesis; Reverse Transcriptase Polymerase Chain Reaction; Tumors of the respiratory system and mediastinum
• ISSN: 1078-0432; 1557-3265

Amplification and/or overexpression of HER2/neu have been documented in many types of epithelial tumor, and HER2/neu evaluation is now gaining importance, because this mechanisms of disease can be inhibited in vivo using humanized monoclonal antibodies. The main purpose of our investigation includes the evaluation of the prevalence of HER2/neu alterations in non-small cell lung cancer (NSCLC) at different molecular levels. We performed a comprehensive investigation of HER2/neu alterations in a series of 115 NSCLC, using fluorescence in situ hybridization (FISH), real time reverse transcription (RT)-PCR, and immunohistochemistry. HER2/neu immunoreactivity was detected in 26 of 115 of specimens (23%), with 5 carcinomas (4%) showing intense staining. Real time RT-PCR demonstrated HER2/neu mRNA in all samples analyzed, with levels above normal in 54 of 115 of carcinomas (47%). FISH documented HER2/neu gene amplification in 9 of 41 carcinomas (22%). These results demonstrate that HER2/neu alterations occur in NSCLC, albeit with significantly different prevalence depending on the technical assay used for the assessment. It is therefore likely that inhibitory monoclonal antibodies will be appropriate in the treatment of a subgroup of NSCLC patients. The results suggest that other mechanisms unrelated to gene amplification could be responsible for HER2/neu mRNA or protein overexpression. FISH, real time RT-PCR, and immunohistochemistry are complementary techniques for the evaluation of HER2/neu activation, useful for the identification of the subgroup of patients to be treated. The real time RT-PCR assay is very sensitive and requires minimal amounts of tissue for testing, and additional studies should evaluate its clinical application for patient evaluation.