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


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.
Divisions of Pathology and Clinical Laboratories, Japan; Divisions of Pharmaco-Proteomics, Japan; Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
T
T
Mimae
Divisions of Pathology and Clinical Laboratories, Japan. Electronic address: ktsuta@ncc.go.jp.
K
K
Tsuta
Divisions of Pharmaco-Proteomics, Japan.
T
T
Kondo
Department of Medical Innovation, Ventana Medical Systems, Inc., Tucson, USA.
H
H
Nitta
Department of Medical Innovation, Ventana Medical Systems, Inc., Tucson, USA.
T M
TM
Grogan
Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
M
M
Okada
Divisions of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan.
H
H
Asamura
Divisions of Pathology and Clinical Laboratories, Japan.
H
H
Tsuda
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000601:surgery; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D017526:Receptor, IGF Type 1 / Q000235:genetics*; D013945:Thymoma / Q000235:genetics* / Q000601:surgery; D013953:Thymus Neoplasms / Q000235:genetics* / Q000601:surgery
D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D019859:Proto-Oncogene Proteins c-met; D018719:Erb-b2 Receptor Tyrosine Kinases; D017526:Receptor, IGF Type 1; C512478:EGFR protein, human; C508053:ERBB2 protein, human