Thymic epithelial tumors express vascular endothelial growth factors and their receptors as potential targets of antiangiogenic therapy: A tissue micro array-based multicenter study

Rossano Lattanzio, Rossana La Sorda, Francesco Facciolo, Stefano Sioletic, Libero Lauriola, Robert Martucci, Enzo Gallo, Giovannella Palmieri, Amelia Evoli, Gabriele Alessandrini, Luigi Ruco, Erino Angelo Rendina, Mauro Truini, Roberto Chiarle, Antonella Barreca, Achille Pich, Stefano Ascani, Daniele Remotti, Gianni Tunesi, Pierluigi GranoneGiovanni Battista Ratto, Francesco Puma, Edoardo Pescarmona, Mauro Piantelli, Mirella Marino, Sandro Carlini, Virna Cerasoli, Felicita Corzani, Enrico Melis, Massimo Filippetti, Paola Canalini, Giorgio Palestro, Maurizio Lalle, Enrico Ruffini, Anna Ceribelli, Massimo Rinaldi

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: 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). Materials and methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish
Pages (from-to)191-196
Number of pages6
JournalLung Cancer
Volume85
Issue number2
DOIs
Publication statusPublished - 2014

Keywords

  • Biomarkers
  • Thymic epithelial tumors
  • Thymoma
  • Tissue Micro Array
  • Vascular endothelial growth factor
  • Vascular endothelial growth factor receptor

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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