TY - JOUR
T1 - The percentage of Epidermal Growth Factor Receptor (EGFR)-mutated neoplastic cells correlates to response to tyrosine kinase inhibitors in lung adenocarcinoma
AU - De Biase, Dario
AU - Genestreti, Giovenzio
AU - Visani, Michela
AU - Acquaviva, Giorgia
AU - Di Battista, Monica
AU - Cavallo, Giovanna
AU - Paccapelo, Alexandro
AU - Cancellieri, Alessandra
AU - Trisolini, Rocco
AU - Degli Esposti, Roberta
AU - Bartolini, Stefania
AU - Pession, Annalisa
AU - Tallini, Giovanni
AU - Brandes, Alba A.
PY - 2017
Y1 - 2017
N2 - BackgroundEpidermal 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 methodsA 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.ResultsNext 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).ConclusionsThe 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.
AB - BackgroundEpidermal 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 methodsA 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.ResultsNext 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).ConclusionsThe 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.
KW - EGFR
KW - EGFR
UR - http://hdl.handle.net/10807/282297
U2 - 10.1371/journal.pone.0177822
DO - 10.1371/journal.pone.0177822
M3 - Article
SN - 1932-6203
VL - 12
SP - 1
EP - 13
JO - PLoS One
JF - PLoS One
ER -
