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Int J Clin Exp Pathol 2013;6(12):2912-2918

Original Article
HIF-1α and VEGF expression correlates with thrombus remodeling in cases of
intravascular papillary endothelial hyperplasia

Sunzoo Kim, Jae Hun Jun, Jeongshik Kim, Do Won Kim, Yong Hyun Jang, Weon Ju Lee, Ho Yun Chung, Seok-Jong Lee

Departments of Pathology, Dermatology, Plastic Surgery, Kyungpook National University Hospital, Kyungpook National University School of
Medicine, Daegu, South Korea

Received October 1, 2013; Accepted October 15, 2013; Epub November 15, 2013; Published December 1, 2013

Abstract: Intravascular papillary endothelial hyperplasia (IPEH) is histopathologically characterized by endothelium-lined papillary structures
encircling an acellular fibrin core. The process of IPEH pathogenesis is unclear. The purpose of our study was to identify histopathological and
immunohistochemical characteristics of IPEH to better understand the pathogenesis of this disease. After reviewing microscopic and medical
records from Kyungpook National University Hospital, we selected 16 cases of IPEH. Masson’s trichrome and immunohistochemical staining
as well as hematoxylin-eosin staining for 16 cases of IPH were performed. Immunohistochemical studies included CD31, CD68, mast cell
tryptase, hypoxia-inducible factor-1 (HIF-1α), and vascular endothelial growth factor (VEGF). Sections from all our cases showed three distinct
histological regions including a papillary portion with hyalinized fibrous or fibroblastic cores, an area containing an unorganized thrombus, and
organization area with an ingrowth of endothelial cells, myofibroblasts, and fibroblasts. In the organization area, HIF-1α-positive cells were
identified in the loose connective tissue. Endothelial cells forming vascular channels were negative for HIF-1α while VEGF was highly
expressed in both interstitial mononuclear and endothelial cells. In the papillary portion, the cellular cores were strongly positive for both HIF-1α
and VEGF, but the acellular cores were negative. Our investigation confirmed that IPEH is a reactive lesion that incidentally arises during the
organization process of older thrombi. It was also found that HIF-1α and VEGF expression was dependent on the thrombus remodeling stage
in cases of IPEH. (IJCEP1310004).

Keywords: HIF-1α, VEGF, hypoxia, thrombus, intravascular papillary endothelial hyperplasia

Address correspondence to: Dr. Seok-Jong Lee, Department of Dermatology, Kyungpook National University Hospital, Kyungpook National
University School of Medicine, 50 Samduk-dong 2 Ga, Jung-gu, Daegu, South Korea, Zip code: 700-721. Tel: +82-53-200-5834; Fax: +82-53-
426-0770; E-mail: seokjong@knu.ac.kr