title: Concomitant EGFR mutation and ALK rearrangement in lung adenocarcinoma is more frequent than expected: report of a case and review of the literature with demonstration of genes alteration into the same tumor cells.
abstract: Oncogenic drivers in lung non-small-cell lung cancer (NSCLC) are considered mutually exclusive, but a review of the literature reveals that concomitant EGFR mutations and ALK rearrangement may occur in a subset of NSCLC. We report here a case of pulmonary adenocarcinoma with concomitant EGFR mutation in exon 21 (L858R) and ALK rearrangement in naive and relapsed tumors. Tumor cells seem to harbor both gene alterations and the patient had a long-lasting response both to EGFR inhibitor in second line and ALK inhibitor once tumor progressed. A speculative discussion on molecular mechanisms underlying this uncommon phenomenon and practical points about epidemiologic, clinicopathologic features and therapeutic options in this intriguing subset of double-positive tumor are reported.
authors.affiliation: Department of Oncology and Advanced Technologies, Unit of Oncology, Azienda Arcispedale S. Maria Nuova/I.R.C.C.S., Reggio Emilia, Italy. Electronic address: baldi.licia@asmn.re.it.
authors.forename: Licia
authors.initials: L
authors.lastname: Baldi
authors.affiliation: Unit of Pathology, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy.
authors.forename: Maria Cecilia
authors.initials: MC
authors.lastname: Mengoli
authors.affiliation: Department of Oncology and Advanced Technologies, Unit of Pathology, Azienda Arcispedale S. Maria Nuova/I.R.C.C.S., Reggio Emilia, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bisagni
authors.affiliation: Department of Oncology and Advanced Technologies, Unit of Oncology, Azienda Arcispedale S. Maria Nuova/I.R.C.C.S., Reggio Emilia, Italy.
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Banzi
authors.affiliation: Department of Oncology and Advanced Technologies, Unit of Oncology, Azienda Arcispedale S. Maria Nuova/I.R.C.C.S., Reggio Emilia, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Boni
authors.affiliation: Unit of Pathology, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Rossi
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics*; D015321:Gene Rearrangement; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D009154:Mutation; D009367:Neoplasm Staging; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D014057:Tomography, X-Ray Computed
chemical_list: C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases
keywords: ALK; Adenocarcinoma; EGFR; FISH; Immunohistochemistry; Lung; NSCLC