This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Tatematsu, A. Articles by Yatabe, Y. Search for Related Content PubMed PubMed Citation Articles by Tatematsu, A. Articles by Yatabe, Y.

Epidermal Growth Factor Receptor Mutations in Small Cell Lung Cancer

Authors' Affiliations: Departments of ¹ Pathology and Molecular Diagnostics, ² Thoracic Oncology, ³ Thoracic Surgery, Aichi Cancer Center Hospital, ⁴ First Department of Pathology, and ⁵ Department of Pathology, Nagoya University School of Medicine, Nagoya, Japan

Requests for reprints: Yasushi Yatabe, Departments of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan. Phone: 81-52-762-2983; Fax: 81-52-763-5233; E-mail: yyatabezaichi-cc.jp.

Purpose: The vast majority of epidermal growth factor receptor (EGFR) mutations occur in lung adenocarcinoma, and even rare cases of other subtypes with this mutation, such as adenosquamous cell carcinoma, are associated with adenocarcinoma histology. According to this adenocarcinoma-specific nature of EGFR mutation, analysis of EGFR mutations with small cell lung cancers (SCLC) may provide a clue to its histogenesis.

Experimental Design: The mutational status of the EGFR gene was accessed in a cohort of 122 patients with SCLC; all patients were from a single institute. When the EGFR mutated, its gene copy number was also examined.

Results: EGFR mutations were detected in five SCLCs (4%). The patients were mainly in the light smoker and histologic combined subtype. All but one of the tumors harbored gene amplifications. Notably, in three tumors of the combined SCLC subtype, both components of adenocarcinoma and SCLC harbored an EGFR mutation, whereas gene amplification was detected only in the adenocarcinoma component. A partial response was achieved in a patient (with an EGFR mutation) who was treated with gefitinib.

Conclusions: Although EGFR mutations are rare in SCLC, a combined subtype of SCLC with adenocarcinoma in light smokers may have a chance of harboring EGFR mutations. For patients with an EGFR mutation, EGFR tyrosine kinase inhibitor can be a treatment option. In terms of molecular pathogenesis, it is suggested that some SCLCs may have developed from pre-existing adenocarcinomas with EGFR mutations, but the development may not be simply linear, taking into consideration the discordant distribution of EGFR amplification.