title: Small-cell carcinoma with an epidermal growth factor receptor mutation in a never-smoker with gefitinib-responsive adenocarcinoma of the lung.
abstract: Activating mutations in the epidermal growth factor receptor (EGFR) gene are extremely rare in small-cell lung cancer (SCLC). Here, we present a case of an EGFR-mutant gefitinib-responsive non-small-cell lung cancer (NSCLC) of adenocarcinoma histology occurring in a never-smoker followed by subsequent diagnosis of metastatic SCLC carrying an EGFR mutation. Although gefitinib therapy of the primary NSCLC resulted in disease control for over 3 years, the patient subsequently developed metastatic SCLC to the liver. Epidermal growth factor receptor mutation analysis revealed that the exon 21 L858R activating mutation was present in both the original lung adenocarcinoma and the metastatic SCLC. We hypothesize that SCLC either evolved from the previously diagnosed NSCLC or that both arose from a common precursor. Further comparative molecular analysis of these histologically distinct tumors would be of value to better understand the potential role of EGFR in the pathogenesis of SCLC in never-smokers, and the role of selection for an EGFR-mutant SCLC subclone as an unusual mechanism of acquired resistance to EGFR inhibitors in NSCLC.
authors.affiliation: Division of Hematology, Oncology and Transplantation, University of Minnesota Medical School, Minneapolis 55455, USA.
authors.forename: Naheed
authors.initials: N
authors.lastname: Alam
authors.forename: Karen S
authors.initials: KS
authors.lastname: Gustafson
authors.forename: Marc
authors.initials: M
authors.lastname: Ladanyi
authors.forename: Maureen F
authors.initials: MF
authors.lastname: Zakowski
authors.forename: Atul
authors.initials: A
authors.lastname: Kapoor
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Truskinovsky
authors.forename: Arkadiusz Z
authors.initials: AZ
authors.lastname: Dudek
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics*; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D011799:Quinazolines / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib