Expression and Mutation Statuses of Epidermal Growth Factor Receptor in Thymic Epithelial Tumors

Background: Epidermal growth factor receptor (EGFR) gene mutations have been reported to correlate with the sensitivity to the tyrosine kinase inhibitor treatment for advanced lung cancers. Since several reports have shown that invasive thymoma overexpress the EGFR protein, we examinedtheEGFRexpressionandmutationstatusesinthymomaandthymiccarcinomatissues. Methods: EGFR mutation statuses from 99 thymic epithelial tumor samples were evaluated by a rapid and sensitive TaqMan assay using Applied Biosysytems 7500 real-time PCR system. Probes were designed according to the 13 different EGFR mutations reported previously in lung cancers. A total of 38 thymoma samples were directly sequenced for the EGFR gene. Protein expressions were evaluated for 56 thymic epithelial tumors by immunohistochemistry. Results: EGFR gene mutations were not detected in any of the thymoma and thymic cancer samples using TaqMan PCR assay. Of the 38 samples 3 showed a heterozygous silent mutation without changes in the protein, a G to A transition at the nucleotide 2361 in exon 18. EGFR expression was significantly higher in invasive thymomas (stages III–IV, 15/19 were positive) than in early stage thymomas (stages I–II, 7/33 were positive) (P < 0.0001). All four carcinomas and all seven B3 thymomas showed EGFR positive staining. Conclusions: Although EGFR mutation at the tyrosine kinase domain is unlikely to be a therapeutictargetforthymoma,theinformationaboutEGFRexpressionwouldcontributetothefurther identification of the therapeutic target for advanced thymomas.