Protein expression and gene copy number changes of receptor tyrosine kinase in thymomas and thymic carcinomas.

Abstract

BACKGROUND:

Insulin-like growth factor-1 receptor (IGF-1R), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-type 2 (HER2), and c-Met are members of the receptor tyrosine kinases (RTKs). The associations between the RTK status [protein expression and gene copy number (GCN)] and patient characteristics and between the RTK status and prognosis remain undetermined.

MATERIALS AND METHODS:

The study included 140 patients who underwent surgery for thymic tumors. Protein expression was evaluated by immunohistochemistry (IHC) and GCN was evaluated by bright-field in situ hybridization (BISH). The correlations between the RTK status and clinicopathological findings were examined.

RESULTS:

IGF-1R protein was frequently detected in thymic carcinoma (83.8%) and EGFR in thymic tumors (91.4%). Thirty-six and 39 tumors were BISH high for IGF-1R and EGFR, respectively: 28 and 25 exhibited high polysomy; 8 and 14 exhibited gene amplification. No tumor was positive for HER2 or c-Met by IHC and BISH. Multivariate analysis revealed that IGF-1R gene amplification (P = 0.027), thymic carcinoma histology, and higher tumor stage were significantly correlated with an adverse prognosis.

CONCLUSIONS:

Thymic epithelial tumors frequently express IGF-1R and/or EGFR proteins. IGF-1R gene amplification is suggested to define an unfavorable subset for thymic epithelial tumors.

• Authors: T Mimae, K Tsuta, T Kondo, H Nitta, T M Grogan, M Okada, H Asamura, H Tsuda
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 23 Issue 12 Pg. 3129-3137 (Dec 2012) ISSN: 1569-8041 [Electronic] England
• PMID: 22700994 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• EGFR protein, human
• ERBB2 protein, human
• ErbB Receptors
• Proto-Oncogene Proteins c-met
• Receptor, ErbB-2
• Receptor, IGF Type 1

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (genetics)
• ErbB Receptors (genetics)
• Female
• Gene Dosage
• Gene Expression
• Gene Expression Regulation, Neoplastic (genetics)
• Humans
• In Situ Hybridization
• Male
• Middle Aged
• Neoplasms, Glandular and Epithelial (genetics, surgery)
• Proto-Oncogene Proteins c-met (genetics)
• Receptor, ErbB-2 (genetics)
• Receptor, IGF Type 1 (genetics)
• Thymoma (genetics, surgery)
• Thymus Neoplasms (genetics, surgery)