Synchronous occurrence of squamous-cell carcinoma "transformation" and EGFR exon 20 S768I mutation as a novel mechanism of resistance in EGFR-mutated lung adenocarcinoma

Lucia Longo; Maria Cecilia Mengoli; Federica Bertolini; Stefania Bettelli; Samantha Manfredini; Giulio Rossi

doi:10.1016/j.lungcan.2016.11.012

Synchronous occurrence of squamous-cell carcinoma "transformation" and EGFR exon 20 S768I mutation as a novel mechanism of resistance in EGFR-mutated lung adenocarcinoma

Lung Cancer. 2017 Jan:103:24-26. doi: 10.1016/j.lungcan.2016.11.012. Epub 2016 Nov 17.

Authors

Lucia Longo¹, Maria Cecilia Mengoli², Federica Bertolini³, Stefania Bettelli², Samantha Manfredini², Giulio Rossi⁴

Affiliations

¹ Medical Oncology Unit, Azienda USL, Hospital "Ramazzini", Carpi, Italy.
² Section of Pathologic Anatomy, Modena University Hospital, Modena, Italy.
³ Department of Oncology, Modena University Hospital, Modena, Italy. Electronic address: [email protected].
⁴ Pathologic Anatomy, Azienda USL Valle d'Aosta, Regional Hospital "Parini", Aosta, Italy.

PMID: 28024692
DOI: 10.1016/j.lungcan.2016.11.012

Abstract

The occurrence of secondary EGFR mutation T790M in exon 20 and histologic "transformation" are common mechanisms underlying resistance to EGFR first- or second-generation tyrosine kinase inhibitors (TKI). We describe here on a hitherto unreported mechanism of EGFR TKI resistance synchronously combining squamous-cell carcinoma change and occurrence of the EGFR exon 20 S768I secondary mutation in a 43 year-old woman with stage IV adenocarcinoma harbouring EGFR exon 21 L858R mutation. After 8 months of response to gefitinib, the patient experienced EGFR TKI resistance and died of leptomeningeal neoplastic dissemination.

Keywords: Adenocarcinoma; EGFR; Lung cancer; Mutation; Squamous cell carcinoma.

Publication types

Case Reports

MeSH terms

Adenocarcinoma / complications
Adenocarcinoma / drug therapy
Adenocarcinoma / genetics*
Adenocarcinoma / pathology
Adenocarcinoma of Lung
Adult
Carcinoma, Non-Small-Cell Lung / complications
Carcinoma, Non-Small-Cell Lung / drug therapy
Carcinoma, Non-Small-Cell Lung / genetics*
Carcinoma, Non-Small-Cell Lung / pathology
Carcinoma, Squamous Cell / complications
Carcinoma, Squamous Cell / drug therapy
Carcinoma, Squamous Cell / genetics*
Carcinoma, Squamous Cell / pathology
Disease Progression
Drug Resistance, Neoplasm / genetics
ErbB Receptors / genetics*
Exons*
Fatal Outcome
Female
Gefitinib
Humans
Lung Neoplasms / complications
Lung Neoplasms / drug therapy
Lung Neoplasms / genetics*
Lung Neoplasms / pathology
Mutation*
Protein Kinase Inhibitors / administration & dosage*
Protein Kinase Inhibitors / therapeutic use
Quinazolines / administration & dosage*
Quinazolines / therapeutic use

Substances

Protein Kinase Inhibitors
Quinazolines
ErbB Receptors
Gefitinib