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

Pathology oncology research: POR

article

Legras, Antoine¹  Fabre, Elizabeth²  Laurent-Puig, Pierre²  Blons, Hélène²  Le Pimpec-Barthes, Françoise¹  Roussel, Hélène⁶  Mangiameli, Giuseppe¹  Arame, Alex¹  Grand, Bertrand¹  Pricopi, Ciprian¹  Badia, Alain¹  Gibault, Laure⁶  Badoual, Cécile⁶ 

[1] Thoracic Surgery and Lung Transplantation Department, Georges Pompidou European Hospital;Saints-Pères Research Center, Paris-Descartes University, Sorbonne Paris Cité University;Medical Thoracic Oncology Department, Georges Pompidou European Hospital;Molecular Biology Department, Georges Pompidou European Hospital;Paris Descartes University;Pathology Department, Georges Pompidou European Hospital;Paris Centre de Recherche Cardiovasculaire, Georges Pompidou European Hospital

关键词: Lung neoplasms;    Lymph nodes;    Genetics;    Biomarkers;    tumour;    High-throughput nucleotide sequencing;   

DOI  :  10.1007/s12253-017-0352-x

来源: Springer

【 摘 要 】

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.

【 授权许可】

Unknown