title: Synchronous occurrence of squamous-cell carcinoma "transformation" and EGFR exon 20 S768I mutation as a novel mechanism of resistance in EGFR-mutated lung adenocarcinoma.
abstract: The occurrence of secondary EGFR mutation T790M in exon 20 and histologic "transformation" are common mechanisms underlying resistance to EGFR first- or second-generation tyrosine kinase inhibitors (TKI). We describe here on a hitherto unreported mechanism of EGFR TKI resistance synchronously combining squamous-cell carcinoma change and occurrence of the EGFR exon 20 S768I secondary mutation in a 43 year-old woman with stage IV adenocarcinoma harbouring EGFR exon 21 L858R mutation. After 8 months of response to gefitinib, the patient experienced EGFR TKI resistance and died of leptomeningeal neoplastic dissemination.
authors.affiliation: Medical Oncology Unit, Azienda USL, Hospital "Ramazzini", Carpi, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Longo
authors.affiliation: Section of Pathologic Anatomy, Modena University Hospital, Modena, Italy.
authors.forename: Maria Cecilia
authors.initials: MC
authors.lastname: Mengoli
authors.affiliation: Department of Oncology, Modena University Hospital, Modena, Italy. Electronic address: bertolini.federica@policlinico.mo.it.
authors.forename: Federica
authors.initials: F
authors.lastname: Bertolini
authors.affiliation: Section of Pathologic Anatomy, Modena University Hospital, Modena, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Bettelli
authors.affiliation: Section of Pathologic Anatomy, Modena University Hospital, Modena, Italy.
authors.forename: Samantha
authors.initials: S
authors.lastname: Manfredini
authors.affiliation: Pathologic Anatomy, Azienda USL Valle d'Aosta, Regional Hospital "Parini", Aosta, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Rossi
mesh_terms: D000230:Adenocarcinoma / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D002289:Carcinoma, Non-Small-Cell Lung / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons; D017809:Fatal Outcome; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D011799:Quinazolines / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib
keywords: Adenocarcinoma; EGFR; Lung cancer; Mutation; Squamous cell carcinoma