Satoshi Saida1, Ken-ichiro Watanabe1, Itaru Kato1, Hisanori Fujino1, Katsutsugu Umeda1, Shinya Okamoto2, Shinji Uemoto2, Tomoro Hishiki3, Hideo Yoshida3, Shiro Tanaka4, Souichi Adachi5, Akira Niwa6, Tatsutoshi Nakahata6, Toshio Heike1. 1. Department of Pediatrics, Kyoto University Graduate School of Medicine, Kyoto, Japan. 2. Division of Hepato-pancreato-biliary Surgery and Transplantation, Kyoto University Graduate School of Medicine, Kyoto, Japan. 3. Department of Pediatric Surgery, Chiba University Graduate School of Medicine, Chiba, Japan. 4. Division of Clinical Trial Design and Management, Translational Research Center, Kyoto University Graduate School of Medicine, Kyoto, Japan. 5. Department of Human Health Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan. 6. Department of Clinical Applications, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
Abstract
BACKGROUND: Hepatoblastoma is a rare childhood malignant tumor that originates from immature hepatic cells. Aminopeptidase-N(CD13), an ectopeptidase that promotes tumor invasion and metastasis, is expressed in fetal stage hepatic progenitor cells, although its role in hepatoblastoma remains unclear. METHODS: The expression pattern of CD13 was investigated on immunohistochemistry in 30 tissue samples from 27 hepatoblastoma patients (16 with predominantly embryonal [pE] histology and 14 with predominantly fetal [pF] histology). Immunoreactive score (IRS) was used to quantify staining data, and the relationship between CD13 expression, clinicopathological factors, and clinical outcome was investigated. The biological function of CD13 was also examined in the hepatoblastoma cell lines Huh6 and HepG2. RESULTS: All specimens stained positive for CD13, with higher CD13 expression in pE than in pF hepatoblastoma samples (median IRS, 4; range, 2-9 vs 2; range, 1-4). Strong CD13 expression was correlated with vascular invasion. Five year event-free survival and overall survival were better in patients with CD13(low) than in those with CD13(high) tumors (100% vs 51.0%, P = 0.026; and 100% vs 74.0%, P = 0.114, respectively). A CD13-neutralizing antibody and the potent CD13 inhibitor, Ubenimex, suppressed invasive activity in HepG2 cells in vitro. CONCLUSIONS: CD13 expression is associated with hepatoblastoma invasiveness and could be a novel prognostic marker for hepatoblastoma.
BACKGROUND:Hepatoblastoma is a rare childhood malignant tumor that originates from immature hepatic cells. Aminopeptidase-N(CD13), an ectopeptidase that promotes tumor invasion and metastasis, is expressed in fetal stage hepatic progenitor cells, although its role in hepatoblastoma remains unclear. METHODS: The expression pattern of CD13 was investigated on immunohistochemistry in 30 tissue samples from 27 hepatoblastomapatients (16 with predominantly embryonal [pE] histology and 14 with predominantly fetal [pF] histology). Immunoreactive score (IRS) was used to quantify staining data, and the relationship between CD13 expression, clinicopathological factors, and clinical outcome was investigated. The biological function of CD13 was also examined in the hepatoblastoma cell lines Huh6 and HepG2. RESULTS: All specimens stained positive for CD13, with higher CD13 expression in pE than in pF hepatoblastoma samples (median IRS, 4; range, 2-9 vs 2; range, 1-4). Strong CD13 expression was correlated with vascular invasion. Five year event-free survival and overall survival were better in patients with CD13(low) than in those with CD13(high) tumors (100% vs 51.0%, P = 0.026; and 100% vs 74.0%, P = 0.114, respectively). A CD13-neutralizing antibody and the potent CD13 inhibitor, Ubenimex, suppressed invasive activity in HepG2 cells in vitro. CONCLUSIONS:CD13 expression is associated with hepatoblastoma invasiveness and could be a novel prognostic marker for hepatoblastoma.
Authors: Juan Manuel Domínguez; Gema Pérez-Chacón; María José Guillén; María José Muñoz-Alonso; Beatriz Somovilla-Crespo; Danay Cibrián; Bárbara Acosta-Iborra; Magdalena Adrados; Cecilia Muñoz-Calleja; Carmen Cuevas; Francisco Sánchez-Madrid; Pablo Avilés; Juan M Zapata Journal: J Hematol Oncol Date: 2020-04-07 Impact factor: 17.388
Authors: Isel Pascual; Pedro A Valiente; Gabriela García; Mario E Valdés-Tresanco; Yarini Arrebola; Lisset Díaz; Lotfi Bounaadja; Rosa María Uribe; Mae Chappé Pacheco; Isabelle Florent; Jean-Louis Charli Journal: Biochimie Date: 2017-09-28 Impact factor: 4.079