Risk of carcinogenesis in the biliary epithelium of children with congenital biliary dilatation through epigenetic and genetic regulation
Risk of carcinogenesis in the biliary epithelium of children with congenital biliary dilatation through epigenetic and genetic regulation
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DOI：
10.1007/s00595-021-02325-2
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发表时间：
2021-06-16
期刊：
影响因子：
2.5
通讯作者：
Shimada，Mitsuo
中科院分区：
文献类型：
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作者：
Mori，Hiroki;Masahata，Kazunori;Shimada，Mitsuo
目的先天性胆管扩张 (CBD) 被定义为伴有胆管扩张的胰胆管连接不良 (PBM)，是胆道癌 (BTC) 的高危因素。据报道，KRAS 和 p53 突变会影响这一过程，但其机制尚不清楚，CBD 儿童在以后的生活中发生 BTC 的可能性也是如此。我们调查了 CBD 儿童与成人相比的潜在致癌途径。 方法本研究的受试者为 9 名 CBD 儿童和 13 名接受肝外胆管切除术的未接受 BTC 的 PBM 成人（10 名扩张，3 名非扩张），以及 4 名因非胆道癌接受胰十二指肠切除术的对照患者。我们采用免疫组化方法检测胆道上皮中 Ki-67、KRAS、p53、组蛋白脱乙酰酶 (HDAC) 和活化诱导胞苷脱氨酶 (AID) 的表达。结果 CBD 儿童和成人胆囊上皮中 Ki-67 标记指数 (LI) 和 KRAS、p53、HDAC 和 AID 的表达均显着升高或呈升高趋势。 PBM 高于对照组。结论 CBD 儿童和 PBM 成人中的 BTC 可能通过 HDAC 和 AID 表达以及表观遗传和基因调控而发育较晚。
PurposesCongenital biliary dilatation (CBD), defined as pancreaticobiliary maljunction (PBM) with biliary dilatation, is a high risk factor for biliary tract cancer (BTC).KRASandp53mutations reportedly affect this process, but the mechanisms are unclear, as is the likelihood of BTC later in life in children with CBD. We investigated potential carcinogenetic pathways in children with CBD compared with adults.MethodsThe subjects of this study were nine children with CBD and 13 adults with PBM (10 dilated, 3 non-dilated) without BTC who underwent extrahepatic bile duct resections, as well as four control patients who underwent pancreaticoduodenectomy for non-biliary cancer. We evaluated expressions of Ki-67, KRAS, p53, histone deacetylase (HDAC) and activation-induced cytidine deaminase (AID) in the biliary tract epithelium immunohistochemically.ResultsThe Ki-67 labeling index (LI) and expressions of KRAS, p53, HDAC, and AID in the gallbladder epithelium were significantly higher or tended to be higher in both the children with CBD and the adults with PBM than in the controls.ConclusionsBTC may develop later in children with CBD and in adults with PBM, via HDAC and AID expression and through epigenetic and genetic regulation.