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


Authors: Alam, N.; Gustafson, K.; Ladanyi, M.; Zakowski, M.; Kapoor, A.; Truskinovsky, A.; Dudek, A.
Article 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.
Keywords: immunohistochemistry; controlled study; human tissue; aged; gene mutation; exon; mutation; histopathology; pathogenesis; case report; cigarette smoking; bevacizumab; cisplatin; erlotinib; drug withdrawal; antineoplastic agents; liver neoplasms; paclitaxel; topotecan; polymerase chain reaction; adenocarcinoma; carboplatin; multiple cycle treatment; lung non small cell cancer; carcinoma, non-small-cell lung; lung neoplasms; epidermal growth factor receptor; receptor, epidermal growth factor; drug effect; lung small cell cancer; lung adenocarcinoma; fluorodeoxyglucose f 18; computer assisted emission tomography; gefitinib; cancer control; drug substitution; quinazolines; cytopenia; retreatment; carcinoma, small cell; egfr mutation; l858r; lrea
Journal Title: Clinical Lung Cancer
Volume: 11
Issue: 5
ISSN: 1525-7304
Publisher: Elsevier Inc.  
Date Published: 2010-09-01
Start Page: E1
End Page: E4
Language: English
DOI: 10.3816/CLC.2010.n.046
PUBMED: 20837450
PROVIDER: scopus
DOI/URL:
Notes: --- - "Export Date: 20 April 2011" - "CODEN: CLCLC" - "Source: Scopus"
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  1. Marc Ladanyi
    1328 Ladanyi
  2. Maureen F Zakowski
    289 Zakowski