title: Thymic epithelial tumors express vascular endothelial growth factors and their receptors as potential targets of antiangiogenic therapy: a tissue micro array-based multicenter study.
abstract: OBJECTIVE
  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).
  
  
  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.
authors.affiliation: Center of Excellence for Research on Ageing, "University G. D'Annunzio" Foundation, Chieti, Italy.
authors.forename: Rossano
authors.initials: R
authors.lastname: Lattanzio
authors.affiliation: Center of Excellence for Research on Ageing, "University G. D'Annunzio" Foundation, Chieti, Italy.
authors.forename: Rossana
authors.initials: R
authors.lastname: La Sorda
authors.affiliation: Thoracic Surgery, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Facciolo
authors.affiliation: Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Sioletic
authors.affiliation: Pathology, Catholic University of Rome, Rome, Italy.
authors.forename: Libero
authors.initials: L
authors.lastname: Lauriola
authors.affiliation: Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Robert
authors.initials: R
authors.lastname: Martucci
authors.affiliation: Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Gallo
authors.affiliation: Molecular and Clinical Endocrinology and Oncology Department, University Federico II, Naples, Italy.
authors.forename: Giovannella
authors.initials: G
authors.lastname: Palmieri
authors.affiliation: Department of Neurosciences, Catholic University of Rome, Rome, Italy.
authors.forename: Amelia
authors.initials: A
authors.lastname: Evoli
authors.affiliation: Thoracic Surgery, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Alessandrini
authors.affiliation: Pathology Unit, Department of Clinical and Molecular Medicine, "Sapienza" University, Sant'Andrea Hospital, Rome, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Ruco
authors.affiliation: Department of Thoracic Surgery, "Sapienza" University, Sant'Andrea Hospital, Rome, Italy.
authors.forename: Erino Angelo
authors.initials: EA
authors.lastname: Rendina
authors.affiliation: Department of Pathology, IRCCS AOU San Martino-IST, National Institute for Cancer Research, Genoa, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Truini
authors.affiliation: Pathology, University of Turin, Turin, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Chiarle
authors.affiliation: Pathology, University of Turin, Turin, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Barreca
authors.affiliation: Pathology, University of Turin, Turin, Italy.
authors.forename: Achille
authors.initials: A
authors.lastname: Pich
authors.affiliation: Institute of Pathological Anatomy, St. Mary Hospital, Perugia University, Terni, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Ascani
authors.affiliation: Pathology, S. Camillo Hospital, Rome, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Remotti
authors.affiliation: Pathology, asl3 genovese Villa Scassi Hospital, Genoa, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Tunesi
authors.affiliation: Thoracic Surgery, Catholic University of Rome, Rome, Italy.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Granone
authors.affiliation: Department of Thoracic Surgery, IRCCS AOU San Martino-IST, National Institute for Cancer Research, Genoa, Italy.
authors.forename: Giovanni Battista
authors.initials: GB
authors.lastname: Ratto
authors.affiliation: Thoracic Surgery, St. Mary Hospital, Terni, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Puma
authors.affiliation: Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Pescarmona
authors.affiliation: Center of Excellence for Research on Ageing, "University G. D'Annunzio" Foundation, Chieti, Italy. Electronic address: mpiantel@unich.it.
authors.forename: Mauro
authors.initials: M
authors.lastname: Piantelli
authors.affiliation: Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy. Electronic address: mirellamarino@inwind.it.
authors.forename: Mirella
authors.initials: M
authors.lastname: Marino
authors.affiliation: Thoracic Surgery, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Carlini
authors.affiliation: Thoracic Surgery, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Virna
authors.initials: V
authors.lastname: Cerasoli
authors.affiliation: Thoracic Surgery, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Felicita
authors.initials: F
authors.lastname: Corzani
authors.affiliation: Thoracic Surgery, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Melis
authors.affiliation: Thoracic Surgery, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippetti
authors.affiliation: Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Canalini
authors.affiliation: Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Palestro
authors.affiliation: Medical Oncology, S. Eugenio Hospital, Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Lalle
authors.affiliation: Thoracic Surgery, University of Turin, Turin, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Ruffini
authors.affiliation: Medical Oncology "A" Department, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Ceribelli
authors.affiliation: Medical Oncology "B" Department, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Rinaldi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers; D002648:Child; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D013953:Thymus Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D015415:Biomarkers; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: Biomarkers; Thymic epithelial tumors; Thymoma; Tissue Micro Array; Vascular endothelial growth factor; Vascular endothelial growth factor receptor