Usefulness of EGFR mutation screening in pleural fluid to predict the clinical outcome of gefitinib treated patients with lung cancer

Junichi Sou, Shinichi Toyooka, Keisuke Aoe, Hiroaki Asano, Syuji Ichihara, Hideki Katayama, Akio Hiraki, Katsuyuki Kiura, Motoi Aoe, Yoshifumi Sano, Kazuro Sugi, Nobuyoshi Shimizu, Hiroshi Date

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

The importance of epidermal growth factor receptor (EGFR) gene mutation has been recognized in nonsmall cell lung cancer (NSCLC), requiring the standardization of mutation screening system including the kind of samples. Here, we examined the EGFR mutation status in 61 pleural fluid samples from NSCLC cases using direct sequencing, nonenriched PCR, mutant-enriched PCR and peptide nucleic acid-locked nucleic acid (PNA-LNA) PCR clamp assay. The mutant-enriched PCR assay detected 16 mutant cases. Among them, the nonenriched PCR assay failed to detect 3 mutant cases. Regarding the discrepancy between mutant-enriched PCR and PNA-LNA PCR clamp assays, 3 cases of exon19-deletions were detected only by mutant-enriched PCR assay and no difference at the L858R mutation. There was no difference in results between direct sequencing and nonenriched PCR assay. We also correlated the EGFR mutation with clinical outcome of gefitinib-treated 29 cases. EGFR mutations were present in 10 cases, revealing 7 partial response and 3 no change (NC). In EGFR wild-type cases, 10 revealed NC and 9 progressive disease. The responders were significantly more frequent among the EGFR mutant cases than among the wild-type (p <0.0001). Overall survival (p = 0.0092) and progression-free survival (p = 0.018) were significantly longer among the EGFR mutant cases than among the wild-type. In summary, we evaluated the utility of EGFR mutation screening in pleural fluid using 4 assays that showed some discrepancies arising from the designs of the assays. As clinical importance, the EGFR mutation status in pleural fluid can be a biomarker for the favorable outcome of gefitinib-treated NSCLC cases.

Original languageEnglish
Pages (from-to)2353-2358
Number of pages6
JournalInternational Journal of Cancer
Volume119
Issue number10
DOIs
Publication statusPublished - Nov 15 2006

Fingerprint

Epidermal Growth Factor Receptor
Lung Neoplasms
Polymerase Chain Reaction
Mutation
Non-Small Cell Lung Carcinoma
Peptide Nucleic Acids
erbB-1 Genes
gefitinib
Disease-Free Survival
Biomarkers
Survival

Keywords

  • EGFR
  • Gefitinib
  • Lung cancer
  • Mutant-enriched PCR
  • Pleural fluid

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Usefulness of EGFR mutation screening in pleural fluid to predict the clinical outcome of gefitinib treated patients with lung cancer. / Sou, Junichi; Toyooka, Shinichi; Aoe, Keisuke; Asano, Hiroaki; Ichihara, Syuji; Katayama, Hideki; Hiraki, Akio; Kiura, Katsuyuki; Aoe, Motoi; Sano, Yoshifumi; Sugi, Kazuro; Shimizu, Nobuyoshi; Date, Hiroshi.

In: International Journal of Cancer, Vol. 119, No. 10, 15.11.2006, p. 2353-2358.

Research output: Contribution to journalArticle

Sou, Junichi ; Toyooka, Shinichi ; Aoe, Keisuke ; Asano, Hiroaki ; Ichihara, Syuji ; Katayama, Hideki ; Hiraki, Akio ; Kiura, Katsuyuki ; Aoe, Motoi ; Sano, Yoshifumi ; Sugi, Kazuro ; Shimizu, Nobuyoshi ; Date, Hiroshi. / Usefulness of EGFR mutation screening in pleural fluid to predict the clinical outcome of gefitinib treated patients with lung cancer. In: International Journal of Cancer. 2006 ; Vol. 119, No. 10. pp. 2353-2358.
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