Follistatin impacts Tumor Angiogenesis and Outcome in Thymic Epithelial Tumors

Abstract

Tumor angiogenesis is a key factor in the progression of thymic epithelial tumors (TETs). Activin A, a member of the TGFβ family, and its antagonist Follistatin are involved in several human malignancies and angiogenesis. We investigated Activin A and Follistatin in serum and tumor tissue of patients with TETs in relation to microvessel density (MVD), WHO histology classification, tumor stage and outcome. Membranous Activin A expression was detected in all tumor tissues of TETs, while Follistatin staining was found in tumor nuclei and cytoplasm. Patients with TETs presented with significantly higher Activin A and Follistatin serum concentrations compared to healthy volunteers, respectively. Follistatin serum concentrations correlated significantly with tumor stage and decreased to physiologic values after complete tumor resection. Follistatin serum concentrations correlated further with MVD and were associated with significantly worse freedom from recurrence (FFR). Low numbers of immature tumor vessels represented even an independent worse prognostic factor for FFR at multivariable analysis. To conclude, the Activin A - Follistatin axis is involved in the pathogenesis of TETs. Further study of Follistatin and Activin A in TETs is warranted as the molecules may serve as targets to inhibit tumor angiogenesis and tumor progression.

Characteristics of genomic mutations and signaling pathway alterations in thymic epithelial tumors

“…TET, a rare malignant tumor of the chest, is the most common anterior mediastinal neoplasm in adults, with an incidence rate of 1.5-3.2 cases per million people per year (36). Among TETs, thymomas are often uniquely associated with autoimmune diseases, whereas thymic carcinomas exhibit more invasive characteristics in clinic.…”

Characteristics of Genomic Mutations and Signaling Pathway Alterations in Thymic Epithelial Tumors

“…TET, a malignant tumor in the chest, is most common, albeit rare, in adult anterior mediastinal neoplasms, with an incidence rate of only 1.5-3.2 cases per 1000,000 people per year . [37] Among TETs, thymomas are often uniquely associated with autoimmune diseases, whereas thymic carcinoma exhibits more invasive characteristics in the clinic. A study by Radovich et al reported a strong association of broad histological subtypes (A, AB, B, and thymic carcinoma) with multiple classes of aberrations that occur at different levels.…”

Clinical relevance of circulating activin A and follistatin in small cell lung cancer

“…In physiological conditions, FST is involved in regulating reproduction, pregnancy, inflammation, metabolism and stress response [30][31][32]44]. Additionally, FST also has a well-known antitumorigenic role [45][46][47]. Chen et al described FST as a novel biomarker for LADC and their findings suggested that circulating FST might be directly secreted by LADC cells in order to neutralize ActA [48].…”