氨肽酶-N（CD13）在肝母细胞瘤中的预后意义。

Prognostic significance of aminopeptidase-N (CD13) in hepatoblastoma.

作者信息

Saida Satoshi, Watanabe Ken-ichiro, Kato Itaru, Fujino Hisanori, Umeda Katsutsugu, Okamoto Shinya, Uemoto Shinji, Hishiki Tomoro, Yoshida Hideo, Tanaka Shiro, Adachi Souichi, Niwa Akira, Nakahata Tatsutoshi, Heike Toshio

机构信息

Department of Pediatrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Division of Hepato-pancreato-biliary Surgery and Transplantation, Kyoto University Graduate School of Medicine, Kyoto, Japan.

出版信息

Pediatr Int. 2015 Aug;57(4):558-66. doi: 10.1111/ped.12597. Epub 2015 Jul 14.

DOI:10.1111/ped.12597

PMID:25682862

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.

摘要

背景

肝母细胞瘤是一种罕见的儿童恶性肿瘤，起源于未成熟的肝细胞。氨肽酶-N（CD13）是一种促进肿瘤侵袭和转移的外肽酶，在胎儿期肝祖细胞中表达，但其在肝母细胞瘤中的作用尚不清楚。

方法

采用免疫组织化学方法研究27例肝母细胞瘤患者（16例主要为胚胎型[pE]组织学类型，14例主要为胎儿型[pF]组织学类型）的30份组织样本中CD13的表达模式。采用免疫反应评分（IRS）对染色数据进行量化，并研究CD13表达、临床病理因素与临床结局之间的关系。还在肝母细胞瘤细胞系Huh6和HepG2中检测了CD13的生物学功能。

结果

所有标本CD13染色均为阳性，pE肝母细胞瘤样本中CD13表达高于pF样本（中位IRS，4；范围，2 - 9 vs 2；范围，1 - 4）。CD13强表达与血管侵犯相关。CD13（低）肿瘤患者的5年无事件生存率和总生存率优于CD13（高）肿瘤患者（分别为100% vs 51.0%，P = 0.026；以及100% vs 74.0%，P = 0.114）。CD13中和抗体和强效CD13抑制剂乌苯美司在体外抑制了HepG2细胞的侵袭活性。