E-cadherin expression and epidermal growth factor receptor mutation status predict outcome in non-small cell lung cancer patients treated with gefitinib

It is known that an epidermal growth factor receptor (EGFR) gene mutation(s) is present in a percentage of non-small cell lung cancers (NSCLCs). Gefitinib, an inhibitor of the tyrosine kinase activity of EGFR, is effective on most of them. The EGFR mutation status alone cannot fully predict the resp...

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Veröffentlicht in:Oncology reports 2008-02, Vol.19 (2), p.377-383
Hauptverfasser: MIYANAGA, Akihiko, GEMMA, Akihiko, TANAKA, Tomoaki, YOSHIMURA, Akinobu, KOBAYASHI, Kunihiko, IWANAMI, Hiroshi, HAGIWARA, Koichi, TSUBOI, Eitaka, KUDOH, Shoji, ANDO, Masahiro, KOSAIHIRA, Seiji, NORO, Rintaro, MINEGISHI, Yuji, KATAOKA, Kiyoko, NARA, Michiya, OKANO, Tetsuya, MIYAZAWA, Hitoshi
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container_issue 2
container_start_page 377
container_title Oncology reports
container_volume 19
creator MIYANAGA, Akihiko
GEMMA, Akihiko
TANAKA, Tomoaki
YOSHIMURA, Akinobu
KOBAYASHI, Kunihiko
IWANAMI, Hiroshi
HAGIWARA, Koichi
TSUBOI, Eitaka
KUDOH, Shoji
ANDO, Masahiro
KOSAIHIRA, Seiji
NORO, Rintaro
MINEGISHI, Yuji
KATAOKA, Kiyoko
NARA, Michiya
OKANO, Tetsuya
MIYAZAWA, Hitoshi
description It is known that an epidermal growth factor receptor (EGFR) gene mutation(s) is present in a percentage of non-small cell lung cancers (NSCLCs). Gefitinib, an inhibitor of the tyrosine kinase activity of EGFR, is effective on most of them. The EGFR mutation status alone cannot fully predict the response to gefitinib and the prognosis for the patients. We hypothesized that information on the expression levels of phosphorylated-EGFR and -Akt, and E-cadherin, alone or in combination with information on the EGFR mutation, may refine our ability of prediction. We investigated 24 NSCLCs that had recurred after surgery and were treated with gefitinib. Specimens resected by surgery were subjected to the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp reaction to determine the EGFR mutation status, and to immunohistochemical staining of phosphorylated-EGFR and -Akt, and E-cadherin to determine their expression levels. The EGFR mutation status was predictive of responsive disease (complete response: CR + partial response: PR) and controlled disease (CR + PR + stable disease: SD). Positive E-cadherin staining was predictive of longer time to progression (12.4 vs. 5.9 months, p
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Positive E-cadherin staining was predictive of longer time to progression (12.4 vs. 5.9 months, p&lt;0.05) and overall survival (OS) (18.4 vs. 13.0 months, p&lt;0.05). Together the patients with an EGFR mutation and the patients with positive E-cadherin staining defined a patient group with a median OS of 18.4 months and excluded the patient group with the median OS of 3.7 months. Neither p-Akt nor p-EGFR staining was associated with the response and survival. 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Gefitinib, an inhibitor of the tyrosine kinase activity of EGFR, is effective on most of them. The EGFR mutation status alone cannot fully predict the response to gefitinib and the prognosis for the patients. We hypothesized that information on the expression levels of phosphorylated-EGFR and -Akt, and E-cadherin, alone or in combination with information on the EGFR mutation, may refine our ability of prediction. We investigated 24 NSCLCs that had recurred after surgery and were treated with gefitinib. Specimens resected by surgery were subjected to the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp reaction to determine the EGFR mutation status, and to immunohistochemical staining of phosphorylated-EGFR and -Akt, and E-cadherin to determine their expression levels. The EGFR mutation status was predictive of responsive disease (complete response: CR + partial response: PR) and controlled disease (CR + PR + stable disease: SD). Positive E-cadherin staining was predictive of longer time to progression (12.4 vs. 5.9 months, p&lt;0.05) and overall survival (OS) (18.4 vs. 13.0 months, p&lt;0.05). Together the patients with an EGFR mutation and the patients with positive E-cadherin staining defined a patient group with a median OS of 18.4 months and excluded the patient group with the median OS of 3.7 months. Neither p-Akt nor p-EGFR staining was associated with the response and survival. In patients with surgically resected NSCLC tumors, the EGFR mutation status and E-cadherin staining can select patients who will benefit from gefitinib therapy.</abstract><cop>Athens</cop><pub>S.n.</pub><pmid>18202784</pmid><doi>10.3892/or.19.2.377</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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subjects Biological and medical sciences
Cadherins - analysis
Cadherins - metabolism
Carcinoma, Non-Small-Cell Lung - drug therapy
DNA Mutational Analysis
Drug Resistance, Neoplasm
Female
Humans
Lung Neoplasms - drug therapy
Male
Medical sciences
Middle Aged
Mutation
Phosphorylation
Pneumology
Prognosis
Protein Kinase Inhibitors - therapeutic use
Proto-Oncogene Proteins c-akt - analysis
Proto-Oncogene Proteins c-akt - metabolism
Quinazolines - therapeutic use
Receptor, Epidermal Growth Factor - antagonists & inhibitors
Receptor, Epidermal Growth Factor - genetics
Treatment Outcome
Tumors
Tumors of the respiratory system and mediastinum
title E-cadherin expression and epidermal growth factor receptor mutation status predict outcome in non-small cell lung cancer patients treated with gefitinib
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