Intratumor heterogeneity of ALK-rearrangements and homogeneity of EGFR-mutations in mixed lung adenocarcinoma

Federica Zito Marino, Giuseppina Liguori, Gabriella Aquino, Elvira La Mantia, Silvano Bosari, Stefano Ferrero, Lorenzo Rosso, Gabriella Gaudioso, Nicla De Rosa, Marianna Scrima, Nicola Martucci, Antonello La Rocca, Nicola Normanno, Alessandro Morabito, Gaetano Rocco, Gerardo Botti, Renato Franco

Research output: Contribution to journalArticle

Abstract

Background Non Small Cell Lung Cancer is a highly heterogeneous tumor. Histologic intratumor heterogeneity could be 'major', characterized by a single tumor showing two different histologic types, and 'minor', due to at least 2 different growth patterns in the same tumor. Therefore, a morphological heterogeneity could reflect an intratumor molecular heterogeneity. To date, few data are reported in literature about molecular features of the mixed adenocarcinoma. The aim of our study was to assess EGFR-mutations and ALK-rearrangements in different intratumor subtypes and/or growth patterns in a series of mixed adenocarcinomas and adenosquamous carcinomas. Methods 590 Non Small Cell Lung Carcinomas tumor samples were revised in order to select mixed adenocarcinomas with available tumor components. Finally, only 105 mixed adenocarcinomas and 17 adenosquamous carcinomas were included in the study for further analyses. Two TMAs were built selecting the different intratumor histotypes. ALK-rearrangements were detected through FISH and IHC, and EGFR-mutations were detected through IHC and confirmed by RT-PCR. Results 10/122 cases were ALK-rearranged and 7 from those 10 showing an intratumor heterogeneity of the rearrangements. 12/122 cases were EGFR-mutated, uniformly expressing the EGFR-mutated protein in all histologic components. Conclusion Our data suggests that EGFR-mutations is generally homogeneously expressed. On the contrary, ALK-rearrangement showed an intratumor heterogeneity in both mixed adenocarcinomas and adenosquamous carcinomas. The intratumor heterogeneity of ALK-rearrangements could lead to a possible impact on the therapeutic responses and the disease outcomes.

Original languageEnglish
Article numbere0139264
JournalPLoS One
Volume10
Issue number9
DOIs
Publication statusPublished - Sep 30 2015

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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