Uncommon EGFR mutations in cytological specimens of 1,874 newly diagnosed indonesian lung cancer patients

Elisna Syahruddin, Laksmi Wulandari, Nunuk Sri Muktiati, Ana Rima, Noni Soeroso, Sabrina Ermayanti, Michael Levi, Heriawaty Hidajat, Grace Widjajahakim, Ahmad Rusdan Handoyo Utomo

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Purpose: We aimed to evaluate the distribution of individual epidermal growth factor receptor (EGFR) mutation subtypes found in routine cytological specimens. Patients and methods: A retrospective audit was performed on EGFR testing results of 1,874 consecutive cytological samples of newly diagnosed or treatment-naïve Indonesian lung cancer patients (years 2015–2016). Testing was performed by ISO15189 accredited central laboratory. Results: Overall test failure rate was 5.1%, with the highest failure (7.1%) observed in pleural effusion and lowest (1.6%) in needle aspiration samples. EGFR mutation frequency was 44.4%. Tyrosine kinase inhibitor (TKI)-sensitive common EGFR mutations (ins/dels exon 19, L858R) and uncommon mutations (G719X, T790M, L861Q) contributed 57.1% and 29%, respectively. Approximately 13.9% of mutation-positive patients carried a mixture of common and uncommon mutations. Women had higher EGFR mutation rate (52.9%) vs men (39.1%; p<0.05). In contrast, uncommon mutations conferring either TKI responsive (G719X, L861Q) or TKI resistance (T790M, exon 20 insertions) were consistently more frequent in men than in women (67.3% vs 32.7% or 69.4% vs 30.6%; p<0.05). Up to 10% EGFR mutation–positive patients had baseline single mutation T790M, exon 20 insertion, or in coexistence with TKI-sensitive mutations. Up to 9% patients had complex or multiple EGFR mutations, whereby 48.7% patients harbored TKI-resistant mutations. One patient presented third-generation TKI-resistant mutation L792F simultaneously with T790M. Conclusion: Routine diagnostic cytological techniques yielded similar success rate to detect EGFR mutations. Uncommon EGFR mutations were frequent events in Indonesian lung cancer patients.

Original languageEnglish
Pages (from-to)25-34
Number of pages10
JournalLung Cancer: Targets and Therapy
Volume9
DOIs
Publication statusPublished - 23 Mar 2018

Keywords

  • Cytology
  • EGFR mutations
  • Indonesia
  • Lung cancer
  • T790M
  • Treatment naive
  • Tyrosine kinase inhibitor

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