Lattanzio Rossano, La Sorda Rossana, Facciolo Francesco, Sioletic Stefano, Lauriola Libero, Martucci Robert, Gallo Enzo, Palmieri Giovannella, Evoli Amelia, Alessandrini Gabriele, Ruco Luigi, Rendina Erino Angelo, Truini Mauro, Chiarle Roberto, Barreca Antonella, Pich Achille, Ascani Stefano, Remotti Daniele, Tunesi Gianni, Granone Pierluigi, Ratto Giovanni Battista, Puma Francesco, Pescarmona Edoardo, Piantelli Mauro, Marino Mirella, Carlini Sandro, Cerasoli Virna, Corzani Felicita, Melis Enrico, Filippetti Massimo, Canalini Paola, Palestro Giorgio, Lalle Maurizio, Ruffini Enrico, Ceribelli Anna, Rinaldi Massimo
Center of Excellence for Research on Ageing, "University G. D'Annunzio" Foundation, Chieti, Italy.
Thoracic Surgery, Regina Elena National Cancer Institute, Rome, Italy.
Lung Cancer. 2014 Aug;85(2):191-6. doi: 10.1016/j.lungcan.2014.05.010. Epub 2014 May 22.
Tumor angiogenesis is an essential and complex process necessary for the growth of all tumors which represents a potential therapeutic target. Angiogenesis inhibitors targeting vascular endothelial growth factor (VEGF) or their receptor tyrosine kinases have been approved by the FDA. In thymic epithelial tumors (TET), targeted therapies have been sporadically applied due to their rarity. To ascertain the presence of potential therapeutic targets, we analyzed by immunohistochemistry the expression of angiogenesis-related biomarkers in a large series of TET arranged in Tissue Micro Arrays (TMA).
We assessed by immunohistochemistry the expression of the possible molecular target of anti-angiogenic therapy, i.e. VEGFA, VEGFC, VEGFD, VEGFR1, VEGFR2, VEGFR3, and PDGFRβ, in a TMA series of 200 TET collected in the framework of a multi-institutional collaborative project for Rare Diseases.
When compared to the low-risk tumors, high-risk TET (B2, B3, carcinomas) contained higher proportion of cancer cells expressing VEGFA, VEGFC and VEGFD (P<0.001, P<0.001, and P<0.001) growth factors, and their receptors VEGFR1 (P=0.002), VEGFR2 (P=0.013), and VEGFR3 (P=0.041). No differences were observed in terms of PDGFRβ expression.
According to our data, it is possible to hypothesize the existence of multiple paracrine and/or autocrine loops in TET, particularly in the high-risk ones, involved in TET growth and progression. Anti-angiogenic agents, directed to inhibit these loops, are therefore to be considered as potential tools in advanced TET therapy.
肿瘤血管生成是所有肿瘤生长所必需的一个重要且复杂的过程，是一个潜在的治疗靶点。靶向血管内皮生长因子（VEGF）或其受体酪氨酸激酶的血管生成抑制剂已获美国食品药品监督管理局（FDA）批准。在胸腺上皮肿瘤（TET）中，由于其罕见性，靶向治疗一直是偶尔应用。为确定潜在治疗靶点的存在情况，我们通过免疫组织化学分析了组织微阵列（TMA）中一系列大量TET中血管生成相关生物标志物的表达。
我们通过免疫组织化学评估了抗血管生成治疗可能的分子靶点，即VEGFA、VEGFC、VEGFD、VEGFR1、VEGFR2、VEGFR3和PDGFRβ在一个由多机构罕见病合作项目收集的200例TET的TMA系列中的表达。
与低风险肿瘤相比，高风险TET（B2、B3、癌）中表达VEGFA、VEGFC和VEGFD（P<0.001、P<0.001和P<0.001）生长因子及其受体VEGFR1（P=0.002）、VEGFR2（P=0.013）和VEGFR3（P=0.041）的癌细胞比例更高。在PDGFRβ表达方面未观察到差异。
根据我们的数据，可以推测在TET中，特别是在高风险TET中，存在多个参与TET生长和进展的旁分泌和/或自分泌环路。因此，旨在抑制这些环路的抗血管生成药物应被视为晚期TET治疗的潜在工具。
