Epidermal growth factor receptor mutations in small cell lung cancer.

Abstract

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.

• Authors: Akiko Tatematsu, Junichi Shimizu, Yoshiko Murakami, Yoshitsugu Horio, Shigeo Nakamura, Toyoaki Hida, Tetsuya Mitsudomi, Yasushi Yatabe
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 14 Issue 19 Pg. 6092-6 (Oct 01 2008) ISSN: 1078-0432 [Print] United States
• PMID: 18829487 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• ErbB Receptors
• Protein-Tyrosine Kinases

Topics

• Adult
• Aged
• Aged, 80 and over
• DNA Mutational Analysis
• Enzyme Inhibitors (pharmacology)
• ErbB Receptors (genetics, physiology)
• Female
• Gene Expression Regulation, Neoplastic
• Genes, erbB-1
• Humans
• Lung Neoplasms (genetics, metabolism)
• Male
• Middle Aged
• Mutation
• Protein-Tyrosine Kinases (antagonists & inhibitors)
• Small Cell Lung Carcinoma (genetics, metabolism)