Protein expression and gene amplification of epidermal growth factor receptor in thymomas.
BACKGROUND
Epidermal growth factor receptor (EGFR) overexpression and amplification are important prognostic factors in many solid tumors and anti-EGFR antibody-based therapy is now available as a promising therapeutic modality. There is little information in the literature regarding the biologic role of EGFR in thymomas that are characterized by variable clinical presentations, histologic heterogeneity, and unpredictable behavior.


METHODS
Protein expression and gene amplification of EGFR were investigated in 32 thymomas (9 World Health Organization [WHO] type A, 5 type AB, 7 type B2, 7 type B3, 4 type C) using immunohistochemistry and fluorescence in situ hybridization (FISH). FISH analysis included assessment of the average number of copies of the EGFR gene per cell, the average ratio of the EGFR gene to chromosome 7 copy numbers, and ploidy.


RESULTS
The results of FISH analysis showed statistically significant correlation with WHO histologic type, invasion, advanced clinical stage, but not with tumor size and outcome. Thymomas associated with myasthenia gravis more frequently showed hyperploidy when compared with sporadic tumors, but there was no difference in EGFR gene amplification. EGFR protein expression assessed by immunohistochemistry did not correlate with any studied clinicopathologic variables. There was poor correlation between the protein expression and gene amplification, only 7 of 23 specimens (30%).


CONCLUSIONS
The potential role of EGFR in the pathogenesis of advanced-stage thymomas indicated that evolving anti-EGFR antibody therapy may be considered as a treatment option.
Ionescu
Diana N
DN
Division of Anatomic Pathology, Department of Pathology, University of Pittsburgh Medical Center, Presbyterian University Hospital, Pittsburgh, Pennsylvania, USA. ionescudn@upmc.edu
Sasatomi
Elizaburo
E
Cieply
Kathleen
K
Nola
Marin
M
Dacic
Sanja
S
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D002897:Chromosomes, Human, Pair 7; D066246:ErbB Receptors / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000379:methods; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000150:complications; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011003:Ploidies; D011237:Predictive Value of Tests; D013945:Thymoma / Q000737:chemistry* / Q000150:complications / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D066246:ErbB Receptors