Disappearance of an activated EGFR mutation after treatment with EGFR tyrosine kinase inhibitors

Abstract

A 34-year-old Japanese woman presented with left supraclavicular lymph node swelling. Computed tomography scans revealed a mass on the left lower lobe, pulmonary nodules, and pleural effusion. A lymph node biopsy revealed large-cell carcinoma with an epidermal growth factor receptor (EGFR) deletion mutation, L747–T751 in exon 19. Although malignant pleural effusions carried the same EGFR mutation, progressive pleural effusions after treatment with chemotherapy, gefitinib, and erlotinib did not show any EGFR mutation. A cell line established from the pleural effusion 3 days before the patient expired also did not harbor the EGFR mutation. Histological sections of the lymph node of the patient were similar to those of the xenograft tumor of the cell line. There may be genetic heterogeneity in EGFR mutant tumors.

Introduction

Lung cancer is the leading cause of cancer deaths worldwide. Although chemotherapy has advanced in the treatment of non-small-cell lung cancer (NSCLC), the prognosis is still poor [1]. Over the last decade, molecular-targeted agents have been introduced in the treatment of NSCLC. Gefitinib and erlotinib are active epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, which have demonstrated significant activity in NSCLC with somatic mutations within the EGFR tyrosine kinase domain [2], [3]. Many new findings have been made using EGFR-mutated lung cancer cell lines [4]. Here, we established a wild-type EGFR lung cancer cell line derived from the patient harboring an activating EGFR mutation and presume that the mutation disappeared after treatment with EGFR tyrosine kinase inhibitors.