Tumor-related gene expression levels in thymic carcinoma and Type B3 thymoma

Abstract

BackgroundThymic carcinoma (TC) is a rare type of malignant neoplasm that develops in the anterior mediastinum and associated with poor prognosis. Type B3 thymoma (B3) occasionally demonstrates malignant tumor characteristics, especially in the advanced stage. We investigated the expressions of tumor-related genes in resected TC and B3 specimens.MethodsTC and B3 specimens resected from 1999 through 2012 were investigated. Tumor segments were collected from the specimens by micro-dissection to extract mRNA, then RT-PCR was performed according to Dannenberg’s tumor profile method for semi-quantitation of tumor-related gene mRNA. To compare with other types of cancer, data from lung cancer (LC) cases in our database were also examined.ResultsThe gene expression levels of thymidylate synthase were significantly higher in TC and B3 as compared to LC specimens (p < 0.02), while no difference were observed between TC and B3 tumors. The ratio of folypolyglutamyl synthase (FPGS) to gamma-glutamyl hydrolase (GGH) mRNA was significantly lower in TC than in B3 (p < 0.05), with lower FPGS/GGH in those tumors related to overall survival. Also, the gene expression of vascular endothelial growth factor (VEGF) was significantly higher in TC as compared to B3 (p = 0.04), with higher VEGF gene expression in TC and B3 specimens related to overall survival of affected patients. Epidermal growth factor receptor (EGFR) expression was significantly higher in B3 as compared to both TC and LC specimens (p < 0.01). However, there were no EGFR gene mutations detected in any of the specimens.ConclusionsThese results indicate that elevated expressions of the tumor-related genes FPGS/GGH and VEGF are correlated with malignancy of TC and B3 tumors. Additional examinations will be necessary to investigate their chemosensitivity.

Case Report of Anlotinib in Advanced Thymic Cancer

“…Due to the large financial burden, the patient Previous research has found that thymoma is associated with multiple gene loci overexpression and mutations [13], such as epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2, Her2), c-kit, vascular endothelial growth factor receptor (VEGFR), insulin-like growth factor 1 receptor (IGF-1R), PDGFR, etc. In particular, the high expression of VEGF [14] and C-KIT is related to the late staging and aggressiveness of thymic cancer, and targeted drugs have entered our field of vision. It is worth noting that EFGR is mainly overexpressed in thymic cancer [15] Anlotinib is a small molecule tyrosine kinase inhibitor independently developed in China, which can simultaneously inhibit VEGFR, PDGFR, FGFR, c-Kit genes and other targets, and has dual effects of anti-angiogenesis and tumor growth.…”

Molecular and Functional Key Features and Oncogenic Drivers in Thymic Carcinomas

“…While drugs like imatinib, sunitinib, and other tyrosine kinase inhibitors with inhibitory activity against KIT have shown anecdotal responses in a few patients, phase II trials of imatinib in non-selected thymic carcinomas have yielded disappointing results [ 33 , 34 ]. EGFR expression is lower in thymic carcinomas compared to thymomas [ 35 ], and somatic mutations in EGFR are infrequent, which explains the limited efficacy of EGFR inhibitors in thymic epithelial tumors [ 36 , 37 ]. Occasional mutations in FGFR2 and FGFR3 have been reported [ 38 ], as well as mutations in PDGFRA [ 28 ].…”

Recent Advances in Pathologic Research and Targeted Therapies of Thymoma

“…Karube Y et al reported folyl polyglutamate synthase (FPGS)/follicle-stimulating hormone (GGH) and vascular endothelial growth factor (VEGF) were elevated in thymic epithelial tumors and the expression levels were correlated with the degree of malignancy of B3 thymomas [50].…”