 Leukemia & Lymphoma, 2013; Early Online: 1–7 © 2013 Informa UK, Ltd. ISSN: 1042-8194 print / 1029-2403 online DOI: 10.3109/10428194.2013.813629 Correspondence: Ipatia A. Doussis-Anagnostopoulou, Department of Histology and Embryology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias str., GR 115 27, Athens, Greece. Tel: + 302107462348. Fax: + 302107462340. E-mail: ipatiada@med.uoa.gr Received 26 February 2013; revised 3 June 2013; accepted 5 June 2013 ORIGINAL ARTICLE: CLINICAL Prognostic significance of immunohistochemical expression of the angiogenic molecules vascular endothelial growth factor-A, vascular endothelial growth factor receptor-1 and vascular endothelial growth factor receptor-2 in patients with classical Hodgkin lymphoma Georgios S. Dimtsas 1 , Eleni C. Georgiadi 1 , Petros Karakitsos 2 , Theodoros P. Vassilakopoulos 3 , Irene Thymara 4 , Penelope Korkolopoulou 4 , Efstratios Patsouris 4 , Christos Kittas 1 & Ipatia A. Doussis-Anagnostopoulou 1 1 Department of Histology and Embryology, 2 Department of Cytopathology, Attikon General University Hospital, 3 Department of Hematology, “Laikon” General Hospital and 4 First Department of Pathology, Medical School, National and Kapodistrian University of Athens, Athens, Greece Introduction Angiogenesis is the process of new blood vessel formation from a pre-existing vascular network by capillary sprouting. his process is implicated in physiological conditions, such as wound healing, tissue repair and ovulation, as well as pathological conditions, such as age-related macular degen- eration, rheumatoid arthritis, psoriasis and tumors [1]. he vascular endothelial growth factor (VEGF) family possesses a central role in angiogenesis, lymphangiogen- esis and vasculogenesis. he family members are VEGF-A [2,3], VEGF-B, VEGF-C, VEGF-D, VEGF-E and placental growth factor (PlGF) [4]. he human VEGF-A gene is the most well characterized and studied gene of the family. It is located at chromosome 6p21.3 [5] and is organized in eight exons, separated by seven introns [6]. Alternative splicing of the gene generates mature isoforms of 121, 165, 189 and 206 amino acids, respectively (VEGF 121 , VEGF 165 , VEGF 189 , VEGF 206 ) [6,7]. VEGF-A, the product of VEGF-A gene, is a 46 kDa molecular weight, heparin-binding homodimeric glycoprotein [3] that acts as a mitogen and survival factor for vascular endothelial cells [3,8], promotes monocyte chemo- taxis [9] and induces vascular leakage [2,10]. VEGF-A exerts its actions by binding two highly related receptor tyrosine kinases, vascular endothelial growth factor receptor-1 (VEGFR-1) (Flt-1) and VEGFR-2 (KDR). Both receptors share the same structure, consisting of seven extracellular immunoglobulin-like domains, a single transmembrane domain and a consensus tyrosine kinase domain interrupted by a kinase insert domain [11,12]. VEGFR-1 has higher ainity for VEGF-A than does VEGFR-2, but in contrast reveals a weaker tyrosine autophosphorylation in response to VEGF-A [13]. VEGFR-1 acts as a negative regulator of angiogenesis during embryogenesis [14], while it stimulates cancer metas- tasis in adulthood [15]. Although VEGFR-2 has lower ain- ity for VEGF-A than that of VEGFR-1, it is the predominant mediator of VEGF-stimulated endothelial cell migration, proliferation, survival and enhanced vascular permeability [16]. VEGFR-2 activation induces Raf–MEK–MAP kinase pathway activation [17]. Abstract Angiogenesis leads to new blood vessel formation and is implicated in both physiological and pathological situations. The vascular endothelial growth factor (VEGF) family is the major mediator of this process. The aim of our study was to evaluate the expression of VEGF-A, vascular endothelial growth factor receptor-1 (VEGFR-1) and VEGFR-2 and their correlation with clinicopathological parameters and prognosis in patients with classical Hodgkin lymphoma (cHL), since the role of angiogenesis in this tumor still remains unclear. The immunohistochemical expression of VEGF-A, VEGFR-1 and VEGFR-2 was examined in 194 patients with cHL. The neoplastic Hodgkin Reed–Sternberg (HRS) cells expressed VEGF-A, VEGFR-1 and VEGFR-2 in 90.3%, 97.2% and 94.1% of cases, respectively. Only the expression of VEGFR-2 was positively correlated with serum albumin levels  4 g/dL. No correlation with patient outcome was observed. All three molecules were statistically correlated with ramiications of blood vessels. Summarizing, our results are not suicient to consider VEGF-A and/or VEGF receptors as prognosticators in cHL. Keywords: Hodgkin lymphoma, angiogenesis, prognosis, VEGF-A, VEGFR-1, VEGFR-2 Leuk Lymphoma Downloaded from informahealthcare.com by Nyu Medical Center on 08/21/13 For personal use only.