Small-cell carcinoma with an epidermal growth factor receptor mutation in a never-smoker with gefitinib-responsive adenocarcinoma of the lung

Naheed Alam, Karen Gustafson, Marc Ladanyi, Maureen Zakowski, Atul Kapoor, Alexander Truskinovsky, Arkadiusz Dudek

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)E1-E4
JournalClinical Lung Cancer
Volume11
Issue number5
DOIs
StatePublished - Sep 1 2010

Keywords

  • EGFR mutation
  • L858R
  • LREA
  • Polymerase chain reaction

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