Lack of prognostic implications of HER-2/neu abnormalities in 345 stage I non-small cell carcinomas (NSCLC) and 207 stage I-III neuroendocrine tumours (NET) of the lung

• Published in: International journal of cancer Vol. 113; no. 1; pp. 101 - 108
• Main Authors: Pelosi, Giuseppe, Del Curto, Barbara, Dell'Orto, Patrizia, Pasini, Felice, Veronesi, Giulia, Spaggiari, Lorenzo, Maisonneuve, Patrick, Iannucci, Antonio, Terzi, Alberto, Lonardoni, Alessandro, Viale, Giuseppe
• Format: Journal Article
• Language: English
• Published: United States 01.01.2005
• Subjects: Adenocarcinoma - genetics; Adolescent; Adult; Aged; Aged, 80 and over; Carcinoma, Neuroendocrine - genetics; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Squamous Cell - genetics; Chromosome Aberrations; Chromosomes, Human, Pair 17; Female; Gene Amplification; Gene Expression Regulation, Neoplastic; Genes, erbB-2; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Middle Aged; Neoplasm Staging; Predictive Value of Tests; Prognosis; Receptor, ErbB-2 - metabolism; Retrospective Studies; Up-Regulation
• ISSN: 0020-7136

HER-2/neu oncogene activation by either gene amplification and/or protein overexpression has been documented in several human malignancies. Irrespective of protein overexpression, HER-2/neu gene amplification is rare in lung cancer and studies on its prevalence and clinicopathological implications in early stage non-small cell lung cancer (NCSLC) and neuroendocrine tumours (NET) of the lung are lacking. We evaluated HER-2/neu abnormalities in 345 Stage I NSCLC and 207 Stage I-III NET of the lung of all the diverse histological types, by using immunohistochemistry and fluorescent in situ hybridization in selected cases. Overall, HER-2/neu immunoreactivity was detected in 23% of 345 NSCLC and in 7% of 207 NET. Gene amplification was seen in only 7 (7.4%) of the immunoreactive tumours, with high-level amplification (HER-2/neu gene to chromosome 17 ratio > 4.0) in 3 adenocarcinomas, 1 squamous-cell carcinoma and 1 large-cell neuroendocrine carcinoma (LCNEC), and low-level amplification (HER-2/neu gene to chromosome 17 ratio from 2.0 to 4.0) in 1 squamous-cell carcinoma and 1 LCNEC. None of tested carcinoids and SCLC showed gene amplification. All but 1 gene amplified case exhibited 2+ or 3+ membrane labeling. No relationship was found between gene amplification or protein overexpression and patients' survival or other clinicopathological variables. HER-2/neu gene amplification and protein overexpression are not closely correlated in lung carcinomas and do not bear any prognostic implication. Among neuroendocrine tumours, LCNEC show a slightly higher prevalence of either HER-2/neu gene amplification or protein overexpression.