Hepatocellular adenoma: new understandings of molecular pathology and novel model of clinical diagnosis and therapy
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摘要: 肝细胞腺瘤(HCA)是最常见的肝细胞性良性肿瘤,病因尚不明确。在西方国家,大多数HCA发生于有长期口服避孕药物史的生育期女性。在2010年新版世界卫生组织肝胆肿瘤组织学分类中,主要根据欧洲国家的研究结果,提出了HCA的4个分子亚型,即Ⅰ型:HNF1α突变失活型;Ⅱ型:β-catenin突变激活型;Ⅲ型:炎症型;Ⅳ型:未分类型。简述了国外HCA分子病理学研究进展,同时还概要介绍了作者新近对189例手术切除HCA的主要研究结果,显示70%的HCA患者为中年男性,50%的患者超重或肥胖,即使女性患者也极少有长期服用避孕药物史;基因测序结果显示,本组HCA的HNF1α基因突变热点和发生频率与欧洲国家报道明显不同,尚未发现β-catenin和gp130基因突变。基于上述结果,认为中国HCA的累及人群和发病机制与欧洲国家有所不同。鉴于文献中已经有HCA恶变的报道,笔者开始探讨对HCA进行基因组微卫星不稳定性或杂合性缺失检测,以评估其分子变异程度,为临床制订相应的治疗策略提供分子病理学依据。Abstract: Hepatocellular adenoma ( HCA) is the most common benign hepatocellular tumor, and its causes remain unclear. In Western countries, HCA is usually seen in the women of reproductive age who have a history of long- term use of oral contraceptives ( OCs) . In the latest 2010 WHO Histological Classification of Hepatobiliary Tumors, which is mainly based on the research results in European countries, it is proposed that HCA is classified into four molecular subtypes, i. e., type I: HNF1α- inactivated HCA; type II: β- catenin- activated HCA; type III: inflammatory HCA; type IV: unclassified HCA. The research progress in the molecular pathology of HCA in foreign countries is reviewed. In addition, the main results of a recent study of 189 patients with HCA who underwent hepatectomy in our hospital are outlined. It was shown that 70% of HCA patients were middle- aged men, and 50% were overweight or obese; even female patients seldom had a history of long- term use of OCs. The gene sequencing showed that the mutational hotspots and frequency of HNF1α in this group of HCA patients were significantly different from those reported in European countries, and no β- catenin and gp130 mutations were found.Therefore, based on the above results, it is considered that the population and pathogenesis of HCA are different in China than in European countries. In light of the reports of malignant transformation of HCA in literature, a feasibility study is conducted to assess the risk of malignant transformation of HCA by detecting the microsatellite instability or loss of heterozygosity, which may provide a molecular pathological basis for developing individualized treatment strategies.
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Key words:
- adenoma, liver cell /
- pathology, clinical
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