Expression profiling and identification of potential molecular targets for therapy in pulmonary large-cell neuroendocrine carcinoma Journal Article


Authors: Iyoda, A.; Travis, W. D.; Sarkaria, I. S.; Jiang, S. X.; Amano, H.; Sato, Y.; Saegusa, M.; Rusch, V. W.; Satoh, Y.
Article Title: Expression profiling and identification of potential molecular targets for therapy in pulmonary large-cell neuroendocrine carcinoma
Abstract: The prognosis for patients with large-cell neuroendocrine carcinoma (LCNEC) of the lung is extremely poor, and an optimal treatment has not yet been established. It has been recently reported that molecular-targeted therapies, such as tyrosine kinase inhibitors for epidermal growth factor receptor (EGFR), are effective in patients with lung carcinoma. In efforts to improve the prognosis of patients with LCNEC, we analyzed gene expression, gene mutations and immunohistochemical (IHC) expression of known molecular targets in LCNECs, and compared the expression to that of lung adenocarcinomas (ACs). Thirteen patients with primary LCNEC and 14 patients with AC were analyzed. We evaluated IHC expression for c-KIT, human epidermal growth factor receptor type 2 (HER2) and vascular endothelial growth factor (VEGF), gene mutations for EGFR, K-ras and c-kit, and gene expression using fluorescence in situ hybridization for EGFR. In cases with LCNEC, the IHC expression of c-KIT, HER2 and VEGF was 76.9, 30.8 and 100%, respectively. There was a significant difference in the IHC expression of c-KIT and HER2 between the LCNEC and AC cases. Two cases of LCNEC had overexpression of HER2, and the frequency of EGFR gene mutations was higher in the the AC group, with only a single EGFR mutation (exon 18) identified in the LCNEC group. Although LCNEC had a higher rate of expression of c-KIT by IHC, no c-kit gene mutations were found. These findings suggest a potential role for anti-VEGF-, anti-c-KIT- and possibly anti-HER2-targeted agents in the treatment of LCNEC. © 2011 Spandidos Publications Ltd.
Keywords: c-kit; vascular endothelial growth factor; therapy; human epidermal growth factor receptor type 2
Journal Title: Experimental and Therapeutic Medicine
Volume: 2
Issue: 6
ISSN: 1792-0981
Publisher: Spandidos Publications  
Date Published: 2011-08-24
Start Page: 1041
End Page: 1045
Language: English
DOI: 10.3892/etm.2011.343
PROVIDER: scopus
PMCID: PMC3440793
PUBMED: 22977617
DOI/URL:
Notes: --- - "Export Date: 3 October 2011" - "Source: Scopus"
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  1. Valerie W Rusch
    865 Rusch
  2. William D Travis
    743 Travis