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Mutational Diversity of Lung Cancer and Associated Lymph Nodes. An Exploratory Prospective Study of 4 Resected cIIIA-N2

  • Antoine Legras
  • Hélène Roussel
  • Giuseppe Mangiameli
  • Alex Arame
  • Bertrand Grand
  • Ciprian Pricopi
  • Alain Badia
  • Laure Gibault
  • Cécile Badoual
  • Elizabeth Fabre
  • Pierre Laurent-Puig
  • Hélène Blons
  • Françoise Le Pimpec-Barthes
Original Article
  • 94 Downloads

Abstract

Mutational heterogeneity could explain different metastatic patterns among IIIA-N2 lung cancer and influence prognosis. The identification of subclonal mutations using deep sequencing to evaluate the degree of molecular heterogeneity may improve IIIA-N2 classification. The aim of this prospective study was to assess mutational and immunohistochemical characteristics in primary tumours and involved lymph nodes (LN) in operated patients. Four patients operated for primary lung carcinoma and unisite N2 mediastinal involvement were consecutively selected. Samples (tumour and paired LN) were analysed for PD1, PD-L1 and CD8 immunostaining. Somatic mutation testing was performed by deep targeted next generation sequencing (NGS), with the AmpliSeq™ Colon and Lung Cancer Panel (LifeTechnology). A total of 9 primary lung cancer samples and 10 LN stations were analysed. For each cancer, we found 2 mutations, with allelic ratios from 3% to 72%. Mutational patterns were heterogeneous for 2 primary tumours. In 3 cases, mutations observed in the primary tumour were not found in LN metastases (ALK, FGFR3, MET). Inversely, in 1 case, a KRAS mutation was found in LN but not in the primary tumour. All primary tumours were found PD-L1 positive while CD8+ T cells infiltrate varied. In the different examined LN samples, PD-L1 expression, CD8+ and PD1+ T cells infiltrate were not similar to the primary tumour. This preliminary prospective study shows the diversity of intra-tumour and LN mutations using routinely-used targeted NGS, concerning both mutated gene and allelic ratio. Further studies are needed to evaluate its prognostic impact.

Keywords

Lung neoplasms Lymph nodes Genetics Biomarkers, tumour High-throughput nucleotide sequencing 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© Arányi Lajos Foundation 2017

Authors and Affiliations

  • Antoine Legras
    • 1
    • 2
  • Hélène Roussel
    • 3
    • 4
  • Giuseppe Mangiameli
    • 1
  • Alex Arame
    • 1
  • Bertrand Grand
    • 1
  • Ciprian Pricopi
    • 1
  • Alain Badia
    • 1
  • Laure Gibault
    • 3
  • Cécile Badoual
    • 3
    • 4
  • Elizabeth Fabre
    • 2
    • 5
  • Pierre Laurent-Puig
    • 2
    • 6
  • Hélène Blons
    • 2
    • 6
  • Françoise Le Pimpec-Barthes
    • 1
    • 7
  1. 1.Thoracic Surgery and Lung Transplantation Department, Georges Pompidou European HospitalAssistance Publique Hôpitaux de ParisParis Cedex 15France
  2. 2.INSERM UMR-S1147, CNRS SNC 5014, Saints-Pères Research CenterParis-Descartes University, Sorbonne Paris Cité UniversityParisFrance
  3. 3.Pathology Department, Georges Pompidou European HospitalAssistance Publique Hôpitaux de ParisParisFrance
  4. 4.INSERM UMR-S970, Paris Centre de Recherche CardiovasculaireGeorges Pompidou European HospitalParisFrance
  5. 5.Medical Thoracic Oncology Department, Georges Pompidou European HospitalAssistance Publique Hôpitaux de ParisParisFrance
  6. 6.Molecular Biology Department, Georges Pompidou European HospitalAssistance Publique Hôpitaux de ParisParisFrance
  7. 7.INSERM UMR-S1162, 27 rue Juliette DoduParis Descartes UniversityAlli in ParisFrance

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