title: 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.
abstract: 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.
authors.affiliation: Division of Pathology and Laboratory Medicine, European Institute of Oncology and University of Milan School of Medicine, Milan, Italy. giuseppe.pelosi@ieo.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pelosi
authors.forename: Barbara
authors.initials: B
authors.lastname: Del Curto
authors.forename: Patrizia
authors.initials: P
authors.lastname: Dell'Orto
authors.forename: Felice
authors.initials: F
authors.lastname: Pasini
authors.forename: Giulia
authors.initials: G
authors.lastname: Veronesi
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Spaggiari
authors.forename: Patrick
authors.initials: P
authors.lastname: Maisonneuve
authors.forename: Antonio
authors.initials: A
authors.lastname: Iannucci
authors.forename: Alberto
authors.initials: A
authors.lastname: Terzi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Lonardoni
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viale
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018278:Carcinoma, Neuroendocrine / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012189:Retrospective Studies; D015854:Up-Regulation
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases