Overexpression of YAP1 in EGFR mutant lung adenocarcinoma prior to tyrosine kinase inhibitor therapy is associated with poor survival

EGFR tyrosine kinase inhibitor (EGFR TKI) is approved as first-line treatment for advanced-stage EGFR mutant lung adenocarcinoma (LADC). Yes-associated protein 1 (YAP1), a main effector of the Hippo pathway, is associated with adverse prognosis and disruption of EGFR TKI modulation of non-small cell...

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Bibliographic Details
Published in:Pathology, research and practice research and practice, 2018-03, Vol.214 (3), p.335-342
Main Authors: Hong, Soon Auck, Jang, Si-Hyong, Oh, Mee-Hye, Kim, Sung Joon, Kang, Jin-Hyung, Hong, Sook-Hee
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - genetics
Adenocarcinoma - genetics
Adenocarcinoma - mortality
Adenocarcinoma - pathology
Adenocarcinoma of Lung
Adult
Aged
Aged, 80 and over
Carcinoma, Non-Small-Cell Lung - drug therapy
Carcinoma, Non-Small-Cell Lung - pathology
Disease-Free Survival
Drug Resistance, Neoplasm - drug effects
EGFR tyrosine kinase inhibitor
ErbB Receptors - genetics
ErbB Receptors - metabolism
Female
Humans
Lung adenocarcinoma
Lung Neoplasms - drug therapy
Lung Neoplasms - genetics
Lung Neoplasms - mortality
Lung Neoplasms - pathology
Male
Middle Aged
Mutation - genetics
Phosphoproteins - genetics
Prognosis
Protein Kinase Inhibitors - therapeutic use
Transcription Factors
YAP1
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Summary:EGFR tyrosine kinase inhibitor (EGFR TKI) is approved as first-line treatment for advanced-stage EGFR mutant lung adenocarcinoma (LADC). Yes-associated protein 1 (YAP1), a main effector of the Hippo pathway, is associated with adverse prognosis and disruption of EGFR TKI modulation of non-small cell lung cancer. In this study, we demonstrated a prognostic role of YAP1 in EGFR mutant LADC and efficacy of EGFR TKI therapy. A total of 63 patients, including 41 with paired lung cancer specimens before and after EGFR TKI therapy and 22 with non-paired lung cancer specimens prior to EGFR TKI, were enrolled for examination. Expression of YAP1 protein was evaluated using immunohistochemistry. Fifteen paired cases (36.6%) with high nuclear YAP1 expression were detected in the pre-EGFR TKI LADC group and 21 paired cases (52.5%) after treatment with EGFR TKI. Nuclear YAP1 expression was significantly upregulated after EGFR TKI therapy (P = .002). Fifteen paired cases with high nuclear YAP1 expression before EGFR TKI LADCs showed poorer overall survival (OS) (P = .023) and progression-free survival (PFS) (P = .041). Among the 63 patients under study, those with high nuclear YAP1 expression before EGFR TKI showed shorter OS (P = .038) and PFS (P 
ISSN:0344-0338
1618-0631
DOI:10.1016/j.prp.2018.01.010