Open AccessThe percentage of Epidermal Growth Factor Receptor (EGFR)-mutated neoplastic cells correlates to response to tyrosine kinase inhibitors in lung adenocarcinoma
Author(s) -
Dario de Biase,
Giovenzio Genestreti,
Michela Visani,
Giorgia Acquaviva,
Monica Di Battista,
Giovanna Cavallo,
Alexandro Paccapelo,
Alessandra Cancellieri,
Rocco Trisolini,
R Degli Esposti,
Stefania Bartolini,
Annalisa Pession,
Giovanni Tallini,
Alba Ariela Brandes
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0177822
Subject(s) - epidermal growth factor receptor , adenocarcinoma , lung cancer , cancer research , biology , exon , neoplastic cell , tyrosine kinase , adenocarcinoma of the lung , cancer , oncology , medicine , receptor , cell , gene , genetics
Background Epidermal Growth Factor Receptor ( EGFR) molecular analysis is performed to assess the responsiveness to Tyrosine Kinase Inhibitors (TKIs) in patients with Non-Small Cell Lung Cancer (NSCLC). The existence of molecular intra-tumoral heterogeneity has been observed in lung cancers. The aim of the present study is to investigate if the percentage of mutated neoplastic cells within the tumor sample might influence the responsiveness to TKIs treatment. Material and methods A total of 931 cases of NSCLC were analyzed for EGFR mutational status (exon 18, 19, 20, 21) using Next Generation Sequencer. The percentage of mutated neoplastic cells was calculated after normalizing the percentage of mutated alleles obtained after next generation sequencer analysis with the percentage of neoplastic cells in each tumor. Results Next generation sequencing revealed an EGFR mutation in 167 samples (17.9%), mainly deletions in exon 19. In 18 patients treated with TKIs and with available follow-up, there was a significant correlation between the percentage of mutated neoplastic cells and the clinical response (P = 0.017). Patients with a percentage of mutated neoplastic cells greater than 56%, have a statistical trend (P = 0.081) for higher Overall Survival (26.3 months) when compared to those with a rate of mutated neoplastic cells lower than 56% (8.2 months). Conclusions The percentage of EGFR -mutated neoplastic cells in the tumor is associated with response to TKIs. A “quantitative result” of EGFR mutational status might provide useful information in order to recognize those patients which might have the greatest benefit from TKIs.