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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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 |
doi_str_mv | 10.3892/or.19.2.377 |
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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<0.05) and overall survival (OS) (18.4 vs. 13.0 months, p<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.</description><identifier>ISSN: 1021-335X</identifier><identifier>EISSN: 1791-2431</identifier><identifier>DOI: 10.3892/or.19.2.377</identifier><identifier>PMID: 18202784</identifier><language>eng</language><publisher>Athens: S.n.</publisher><subject>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</subject><ispartof>Oncology reports, 2008-02, Vol.19 (2), p.377-383</ispartof><rights>2008 INIST-CNRS</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20032604$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18202784$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MIYANAGA, Akihiko</creatorcontrib><creatorcontrib>GEMMA, Akihiko</creatorcontrib><creatorcontrib>TANAKA, Tomoaki</creatorcontrib><creatorcontrib>YOSHIMURA, Akinobu</creatorcontrib><creatorcontrib>KOBAYASHI, Kunihiko</creatorcontrib><creatorcontrib>IWANAMI, Hiroshi</creatorcontrib><creatorcontrib>HAGIWARA, Koichi</creatorcontrib><creatorcontrib>TSUBOI, Eitaka</creatorcontrib><creatorcontrib>KUDOH, Shoji</creatorcontrib><creatorcontrib>ANDO, Masahiro</creatorcontrib><creatorcontrib>KOSAIHIRA, Seiji</creatorcontrib><creatorcontrib>NORO, Rintaro</creatorcontrib><creatorcontrib>MINEGISHI, Yuji</creatorcontrib><creatorcontrib>KATAOKA, Kiyoko</creatorcontrib><creatorcontrib>NARA, Michiya</creatorcontrib><creatorcontrib>OKANO, Tetsuya</creatorcontrib><creatorcontrib>MIYAZAWA, Hitoshi</creatorcontrib><title>E-cadherin expression and epidermal growth factor receptor mutation status predict outcome in non-small cell lung cancer patients treated with gefitinib</title><title>Oncology reports</title><addtitle>Oncol Rep</addtitle><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<0.05) and overall survival (OS) (18.4 vs. 13.0 months, p<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.</description><subject>Biological and medical sciences</subject><subject>Cadherins - analysis</subject><subject>Cadherins - metabolism</subject><subject>Carcinoma, Non-Small-Cell Lung - drug therapy</subject><subject>DNA Mutational Analysis</subject><subject>Drug Resistance, Neoplasm</subject><subject>Female</subject><subject>Humans</subject><subject>Lung Neoplasms - drug therapy</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Phosphorylation</subject><subject>Pneumology</subject><subject>Prognosis</subject><subject>Protein Kinase Inhibitors - therapeutic use</subject><subject>Proto-Oncogene Proteins c-akt - analysis</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Quinazolines - therapeutic use</subject><subject>Receptor, Epidermal Growth Factor - antagonists & inhibitors</subject><subject>Receptor, Epidermal Growth Factor - genetics</subject><subject>Treatment Outcome</subject><subject>Tumors</subject><subject>Tumors of the respiratory system and mediastinum</subject><issn>1021-335X</issn><issn>1791-2431</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkTtrHTEQhUVIiB9JlT6oiRuz13pd7ao0xnmAIU0C6YRWGl0r7EprSYudf-Kfa118scs0M6f45swwB6FPlGz4oNhFyhuqNmzD-_4NOqa9oh0TnL5tmjDacb79c4ROSvlLCOuJVO_RER1Y04M4Ro_XnTXuFnKIGB6WDKWEFLGJDsMSHOTZTHiX0329xd7YmjLOYGHZi3mtpu7p0vpacJt2wVac1mrTDLhZxhS70iwmbKGVaY07bE20kPHSZiHWgmsGU8Hh-9B27MCHGmIYP6B33kwFPh76Kfr99frX1ffu5ue3H1eXN53lgteOgzSeOkVBjoIPxrjtOCgvhe_ZljPVc2nJQGHwo-VmdNQ4oNYrT0VjheCn6OzZd8npboVS9RzK_lgTIa1F94QxLoX8L8iIFG0bb-D5M2hzKiWD10sOs8n_NCV6n5hOWVOlmW6JNfrzwXYdZ3Cv7CGiBnw5AKZYM_nc3hfKC8cI4UwSwZ8AvMCi5A</recordid><startdate>20080201</startdate><enddate>20080201</enddate><creator>MIYANAGA, Akihiko</creator><creator>GEMMA, Akihiko</creator><creator>TANAKA, Tomoaki</creator><creator>YOSHIMURA, Akinobu</creator><creator>KOBAYASHI, Kunihiko</creator><creator>IWANAMI, Hiroshi</creator><creator>HAGIWARA, Koichi</creator><creator>TSUBOI, Eitaka</creator><creator>KUDOH, Shoji</creator><creator>ANDO, Masahiro</creator><creator>KOSAIHIRA, Seiji</creator><creator>NORO, Rintaro</creator><creator>MINEGISHI, Yuji</creator><creator>KATAOKA, Kiyoko</creator><creator>NARA, Michiya</creator><creator>OKANO, Tetsuya</creator><creator>MIYAZAWA, Hitoshi</creator><general>S.n.</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20080201</creationdate><title>E-cadherin expression and epidermal growth factor receptor mutation status predict outcome in non-small cell lung cancer patients treated with gefitinib</title><author>MIYANAGA, Akihiko ; 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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<0.05) and overall survival (OS) (18.4 vs. 13.0 months, p<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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