INTRODUCTION: Recent studies suggested that p95HER2, the NH2-terminally truncated form of human epidermal growth factor receptor 2 (HER2), could confer resistance to monoclonal antibodies against HER2 (HER2-mab). The aim of this study was to investigate the role of p95HER2 according to HER2 gene copy number (GCN) and HER2 mutation in non-small cell lung cancer (NSCLC). METHODS: The study included 447 resected NSCLC patients evaluated for P95HER2 status by immunofluorescence. Data were correlated with HER2 GCN evaluated by fluorescence in situ hybridization (FISH) and HER2 mutations. Tumors were scored as positive for p95HER2 expression if any cytoplasmic staining was detected. RESULTS: P95HER2 was successfully evaluated in 431 patients and was positive (p95HER2+) in 33 (7.6%) cases. HER2 GCN was evaluable in 439 patients, and increased GCN (at least four copies in at least 40% cells) was found in 60 cases, of which 22 (5.0%) displayed gene amplification (GA). Among the 22 patients with HER2 amplification, only one resulted P95HER2+. To further investigate whether the receptor is truncated in presence of gene mutation, in addition to the study cohort, we analyzed p95HER2 status in eight NSCLC samples harboring HER2 mutation, and only one case resulted p95HER2+. In the whole population, p95HER2- patients had numerically higher risk of death than p95HER2+ (hazard ratio = 1.4, p = 0.2). No difference in survival was observed between patients with or without HER2 GA (median 38 versus 41 months, p = 0.46). HER2 GA was significantly associated with EGFR and MET GA, with no effect on survival. CONCLUSIONS: HER2 truncation and HER2 increased GCN are not prognostic in resected NSCLC. P95HER2 is a very rare event in individuals displaying HER2 gene amplification or mutation.
INTRODUCTION: Recent studies suggested that p95HER2, the NH2-terminally truncated form of human epidermal growth factor receptor 2 (HER2), could confer resistance to monoclonal antibodies against HER2 (HER2-mab). The aim of this study was to investigate the role of p95HER2 according to HER2 gene copy number (GCN) and HER2 mutation in non-small cell lung cancer (NSCLC). METHODS: The study included 447 resected NSCLCpatients evaluated for P95HER2 status by immunofluorescence. Data were correlated with HER2 GCN evaluated by fluorescence in situ hybridization (FISH) and HER2 mutations. Tumors were scored as positive for p95HER2 expression if any cytoplasmic staining was detected. RESULTS: P95HER2 was successfully evaluated in 431 patients and was positive (p95HER2+) in 33 (7.6%) cases. HER2 GCN was evaluable in 439 patients, and increased GCN (at least four copies in at least 40% cells) was found in 60 cases, of which 22 (5.0%) displayed gene amplification (GA). Among the 22 patients with HER2 amplification, only one resulted P95HER2+. To further investigate whether the receptor is truncated in presence of gene mutation, in addition to the study cohort, we analyzed p95HER2 status in eight NSCLC samples harboring HER2 mutation, and only one case resulted p95HER2+. In the whole population, p95HER2- patients had numerically higher risk of death than p95HER2+ (hazard ratio = 1.4, p = 0.2). No difference in survival was observed between patients with or without HER2 GA (median 38 versus 41 months, p = 0.46). HER2 GA was significantly associated with EGFR and MET GA, with no effect on survival. CONCLUSIONS:HER2 truncation and HER2 increased GCN are not prognostic in resected NSCLC. P95HER2 is a very rare event in individuals displaying HER2 gene amplification or mutation.
Authors: D J Slamon; W Godolphin; L A Jones; J A Holt; S G Wong; D E Keith; W J Levin; S G Stuart; J Udove; A Ullrich Journal: Science Date: 1989-05-12 Impact factor: 47.728
Authors: Maurizio Scaltriti; Sarat Chandarlapaty; Ludmila Prudkin; Claudia Aura; José Jimenez; Pier Davide Angelini; Gertrudis Sánchez; Marta Guzman; Josep Lluis Parra; Catherine Ellis; Robert Gagnon; Maria Koehler; Henry Gomez; Charles Geyer; David Cameron; Joaquin Arribas; Neal Rosen; José Baselga Journal: Clin Cancer Res Date: 2010-04-20 Impact factor: 12.531
Authors: Miguel A Molina; Rosana Sáez; Elizabeth E Ramsey; María-José Garcia-Barchino; Federico Rojo; Adam J Evans; Joan Albanell; Edward J Keenan; Ana Lluch; Javier García-Conde; José Baselga; Gail M Clinton Journal: Clin Cancer Res Date: 2002-02 Impact factor: 12.531
Authors: Ralph G Zinner; Bonnie S Glisson; Frank V Fossella; Katherine M W Pisters; Merril S Kies; Pamela M Lee; Erminia Massarelli; Bradley Sabloff; Herbert A Fritsche; Jae Y Ro; Nelson G Ordonez; Hai T Tran; Ying Yang; Terry L Smith; Robert D Mass; Roy S Herbst Journal: Lung Cancer Date: 2004-04 Impact factor: 5.705
Authors: Kim Pedersen; Pier-Davide Angelini; Sirle Laos; Alba Bach-Faig; Matthew P Cunningham; Cristina Ferrer-Ramón; Antonio Luque-García; Jesús García-Castillo; Josep Lluis Parra-Palau; Maurizio Scaltriti; Santiago Ramón y Cajal; José Baselga; Joaquín Arribas Journal: Mol Cell Biol Date: 2009-04-13 Impact factor: 4.272
Authors: M G Kris; D R Camidge; G Giaccone; T Hida; B T Li; J O'Connell; I Taylor; H Zhang; M E Arcila; Z Goldberg; P A Jänne Journal: Ann Oncol Date: 2015-04-21 Impact factor: 32.976