Unique genetic alterations and clinicopathological features of hepatocellular adenoma in Chinese population
Unique genetic alterations and clinicopathological features of hepatocellular adenoma in Chinese population
复制标题
DOI：
10.1016/j.prp.2015.09.003
复制
发表时间：
2015-01-01
影响因子：
2.8
通讯作者：
Wu, Meng-Chao
中科院分区：
文献类型：
--
作者：
Liu, Hai-Ping;Zhao, Qian;Wu, Meng-Chao
肝细胞腺瘤（HCA）是一种良性肝细胞源性肿瘤，常见于欧洲和北美国家长期使用口服避孕药（OC）的育龄妇女。因此，HCA目前被世界卫生组织分为四种分子亚型。本研究首次对中国最大的HCA系列进行了遗传学和临床病理学特征的研究。我们回顾了1984年1月至2012年1月在我院肝脏中心接受肝切除术的189例HCA患者，其中36例HCA随机选择进行HNF 1 α，β-catenin和gp 130基因测序，60例HCA随机选择进行微卫星不稳定性（MSI）检测。与西方研究相比，我们的数据显示了不同的结果，包括男性（69.8%）和超重/肥胖（50.3%）的优势。只有3.5%的女性患者有2-4年的口服避孕药使用史。36例HCA均存在HNF 1 α突变（72%错义，28%同义），17例（47%）和10例（27.8%）HNF 1 α存在2个热点多态性（I27 L：rs 1169288和S487 N：rs 2464196），HNF 1 α第9内含子存在1个新的单核苷酸多态性位点（rs 1169304）。32例（88%）检测到β-catenin基因，免疫组化未检测到β-catenin和gp 130基因突变，也未检测到β-catenin核染色。在34例超重/肥胖HCA患者中，D1251398（HNF 1 α失活通路）和D 6S 1064（HIPPO信号通路）的MSI频率分别为75%和78.5%。我们的研究结果首次表明，中国HCA患者多发生在男性超重和肥胖的成年人群中，与OC使用无关，并表现出独特的遗传改变。这些结果表明，中国HCA患者的肿瘤发生可能与其他致病途径有关。(C)2015 Elsevier GmbH. All rights reserved.
Hepatocellular adenoma (HCA) is a benign hepatocyte-derived tumor commonly seen in reproductive-aged women with long-term use of oral contraceptives (OCs) in European and North American countries. Accordingly, HCA is currently classified into four molecular subtypes as adopted by the World Health Organization. The present study was firstly to characterize and determine the genetic alterations and clinicopathological features of the largest series of HCAs in China. We reviewed 189 patients with HCA who underwent hepatectomies at our liver center from January 1984 to January 2012, among which 36 HCAs were randomly selected for the sequencing of HNF1 alpha, beta-catenin and gp130 genes, and 60 HCAs were randomly selected for detecting microsatellite instability (MSI). Compared with Western studies, our data showed distinctive findings including male (69.8%) and overweight/obese (50.3%) predominance. Only 3.5% of female patients had a documented history of OCs use for 2-4 years. All 36 sequenced HCAs showed HNF1 alpha mutations (72% missense, 28% synonymous), 2 hotspot polymorphisms of HNF1 alpha (I27L: rs1169288 and S487N: rs2464196) were seen in 17(47%) and 10(27.8%) cases, respectively, and a novel single nucleotide polymorphism site (rs1169304) in intron 9 of HNF1 alpha. was detected in 32(88%) cases, but no beta-catenin or gp130 gene mutation was detected, and no nuclear beta-catenin staining was detected by immunohistochemistry. The frequency of MSI was 75% for D1251398 (HNF1 alpha inactivated pathway) and 78.5% for D6S1064 (HIPPO signaling pathway) in 34 overweight/obese patients with HCA. Our results firstly indicate that patients with HCA in China frequently occur in male overweigh and obese adult population, lack an association with OCs use and exhibit unique genetic alterations. Taken together, these observations suggest that alternative pathogenetic pathways involve in HCA tumorigenesis in Chinese patients. (C) 2015 Elsevier GmbH. All rights reserved.