Variations in molecular profile in NSCLC can be analyzed using cytological samples: development of EGFR resistance mutations and coexistence of ALK-EML4 translocation in an EGFR-sensitive patient

Int J Surg Pathol. 2015 Apr;23(2):111-5. doi: 10.1177/1066896914539551. Epub 2014 Jun 17.

Abstract

As a result of therapeutic advances, a revolution is taking place in the lung cancer field with major implications for pathologic diagnosis and tissue management. We report a case of a non-small cell lung carcinoma patient with coexistence of EGFR mutations and ALK-EML4 rearrangements that responded to EGFR inhibitors and in which the development of a new resistance mutation in exon 20 of EGFR-determined treatment resistance. All the molecular determinations were performed in cytological samples. To our knowledge, this is the first case reported with these characteristics, and the 11th case described with coexistence of EGFR mutations and ALK-EML4 rearrangements. The EGFR L858R mutation in exon 21 was found at diagnosis, and the patient presented a 4-year response to erlotinib. On progression, the T790M resistance mutation in the EGFR exon 20 was also confirmed in cytological samples. At this point, fluorescence in situ hybridization also detected ALK-EML4 translocation. This case emphasizes the usefulness of cytological samples for molecular analysis in lung adenocarcinoma, as well as the relevance of repeating biopsies/fine-needle aspirations in tumor recurrences to assess the mutation profile of the disease.

Keywords: ALK/EML4; EGFR; cytological samples; non–small cell lung cancer (NSCLC).

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Antineoplastic Agents / therapeutic use
  • Biopsy, Fine-Needle
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • DNA Mutational Analysis / methods
  • Drug Resistance, Neoplasm / genetics*
  • ErbB Receptors / genetics*
  • Erlotinib Hydrochloride / therapeutic use
  • Female
  • Humans
  • In Situ Hybridization, Fluorescence
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Mutation*
  • Oncogene Proteins, Fusion / genetics*

Substances

  • Antineoplastic Agents
  • EML4-ALK fusion protein, human
  • Oncogene Proteins, Fusion
  • Erlotinib Hydrochloride
  • EGFR protein, human
  • ErbB Receptors