Source:http://linkedlifedata.com/resource/pubmed/id/19826035
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
21
|
| pubmed:dateCreated |
2009-10-30
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| pubmed:abstractText |
In a subset of lung adenocarcinomas, the epidermal growth factor receptor (EGFR) is activated by kinase domain mutations and/or gene amplification, but the interaction between the two types of abnormalities is complex and unclear. For this study, we selected 99 consecutive never-smoking women of East Asian origin with lung adenocarcinomas that were characterized by histologic subtype. We analyzed EGFR mutations by PCR-capillary sequencing, EGFR copy number abnormalities by fluorescence and chromogenic in situ hybridization and quantitative PCR, and EGFR expression by immunohistochemistry with both specific antibodies against exon 19 deletion-mutated EGFR and total EGFR. We compared molecular and clinicopathologic features with disease-free survival. Lung adenocarcinomas with EGFR amplification had significantly more EGFR exon 19 deletion mutations than adenocarcinomas with disomy, and low and high polysomy (100% versus 54%, P = 0.009). EGFR amplification occurred invariably on the mutated and not the wild-type allele (median mutated/wild-type ratios 14.0 versus 0.33, P = 0.003), was associated with solid histology (P = 0.008), and advanced clinical stage (P = 0.009). EGFR amplification was focally distributed in lung cancer specimens, mostly in regions with solid histology. Patients with EGFR amplification had a significantly worse outcome in univariate analysis (median disease-free survival, 16 versus 31 months, P = 0.01) and when adjusted for stage (P = 0.027). Lung adenocarcinomas with EGFR amplification have a unique association with exon 19 deletion mutations and show distinct clinicopathologic features associated with a significantly worsened prognosis. In these cases, EGFR amplification is heterogeneously distributed, mostly in areas with a solid histology.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/EGFR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/KRAS protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/ras Proteins
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| pubmed:status |
MEDLINE
|
| pubmed:month |
Nov
|
| pubmed:issn |
1538-7445
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| pubmed:author |
pubmed-author:BenedettiniElisaE,
pubmed-author:ChirieacLucian RLR,
pubmed-author:ChouYi-PingYP,
pubmed-author:ChristianiDavid CDC,
pubmed-author:GoanYih-GangYG,
pubmed-author:Holmes-TischAlison JAJ,
pubmed-author:IafrateA JohnAJ,
pubmed-author:JännePasi APA,
pubmed-author:LodaMassimoM,
pubmed-author:SUKhKh,
pubmed-author:ShollLynette MLM,
pubmed-author:WuMing-TsangMT,
pubmed-author:YeapBeow YBY,
pubmed-author:YuJianJ
|
| pubmed:issnType |
Electronic
|
| pubmed:day |
1
|
| pubmed:volume |
69
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
8341-8
|
| pubmed:dateRevised |
2011-5-17
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| pubmed:meshHeading |
pubmed-meshheading:19826035-Adenocarcinoma,
pubmed-meshheading:19826035-Adenocarcinoma, Bronchiolo-Alveolar,
pubmed-meshheading:19826035-Adult,
pubmed-meshheading:19826035-Aged,
pubmed-meshheading:19826035-Carcinoma, Papillary,
pubmed-meshheading:19826035-Female,
pubmed-meshheading:19826035-Gene Amplification,
pubmed-meshheading:19826035-Gene Dosage,
pubmed-meshheading:19826035-Humans,
pubmed-meshheading:19826035-Immunoenzyme Techniques,
pubmed-meshheading:19826035-In Situ Hybridization, Fluorescence,
pubmed-meshheading:19826035-Lung Neoplasms,
pubmed-meshheading:19826035-Male,
pubmed-meshheading:19826035-Middle Aged,
pubmed-meshheading:19826035-Mutation,
pubmed-meshheading:19826035-Prognosis,
pubmed-meshheading:19826035-Proto-Oncogene Proteins,
pubmed-meshheading:19826035-Receptor, Epidermal Growth Factor,
pubmed-meshheading:19826035-Smoking,
pubmed-meshheading:19826035-Survival Rate,
pubmed-meshheading:19826035-ras Proteins
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| pubmed:year |
2009
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| pubmed:articleTitle |
Lung adenocarcinoma with EGFR amplification has distinct clinicopathologic and molecular features in never-smokers.
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| pubmed:affiliation |
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
|