Vascular architecture as diagnostic marker for differentiation of WHO thymoma subtypes and thymic carcinoma.

Thymomas and thymic squamous cell carcinomas (TSQCC) are rare thymic epithelial tumors. Data on angiogenesis and vascular phenotype in these tumors is limited, and no study took histological WHO subtypes into account.,Vascular density, diameter and architecture and expression of SMA, PDGFRb, VEGFR1 and VEGFR2 were investigated in WHO type A, AB, B1, B2 and B3 thymomas and TSQCC, using immuno-stainings, quantitative morphometry and tumor vessel isolation by trypsin digestion. Expression of Ang-1, Ang-2, VEGF-A, PDGF-B and Hif-1α was examined by qRT-PCR.,A and AB thymomas were characterized by a dense network of capillary-like vessels with tight pericyte coverage, while B thymomas showed a loose vascular network with increasing vascular diameters and increasing expression of SMA and PDGFRb from B1 to B3 thymomas and TSQCC. VEGFR1 and VEGFR2 were expressed in vessels of all analyzed tumor entities and at higher levels in epithelial cells of A and B3 thymomas and TSQCC. mRNA of Ang-2, but not Ang-1, was significantly upregulated in all thymoma subtypes, with highest levels in A thymomas. In TSQCC, Ang-1 and VEGF are the predominantly upregulated growth factors. Hif-1α was only upregulated in B3 and TSQCC.,Thymomas and TSQCC differ significantly in their vascular architecture and expression of key angiogenic growth factors. The findings could help to improve the differential diagnosis of difficult-to-classify thymic epithelial tumors and indicate different mechanisms of tumor angiogenesis and functional differences of tumor vessels of major thymoma subtypes and TSQCC. This article is protected by copyright. All rights reserved.