先天性胆管扩张症患儿通过表观遗传和遗传调控导致胆管上皮细胞癌变的风险。
Risk of carcinogenesis in the biliary epithelium of children with congenital biliary dilatation through epigenetic and genetic regulation.
机构信息
Department of Surgery, Institute of Health Biosciences, The University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
Department of Pediatric Surgery, Osaka Women's and Children's Hospital, Murodoucho 840, Izumi, Osaka, 594-1101, Japan.
出版信息
Surg Today. 2022 Feb;52(2):215-223. doi: 10.1007/s00595-021-02325-2. Epub 2021 Jun 16.
PURPOSES
Congenital biliary dilatation (CBD), defined as pancreaticobiliary maljunction (PBM) with biliary dilatation, is a high risk factor for biliary tract cancer (BTC). KRAS and p53 mutations 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.
METHODS
The 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.
RESULTS
The 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.
CONCLUSIONS
BTC may develop later in children with CBD and in adults with PBM, via HDAC and AID expression and through epigenetic and genetic regulation.
目的
先天性胆管扩张症（CBD）定义为胰胆管合流异常伴胆管扩张，是胆管癌（BTC）的一个高危因素。据报道，KRAS 和 p53 突变影响这一过程，但机制尚不清楚，CBD 患儿日后发生 BTC 的可能性也不清楚。我们研究了 CBD 患儿与成人相比可能存在的致癌途径。
方法
本研究的对象为 9 例 CBD 患儿和 13 例成人 PBM（10 例扩张，3 例非扩张）患者，这些患者均因 BTC 以外的疾病接受了肝外胆管切除术，此外还有 4 例因非胆管癌而行胰十二指肠切除术的对照患者。我们通过免疫组织化学评估了胆道上皮细胞中 Ki-67、KRAS、p53、组蛋白去乙酰化酶（HDAC）和激活诱导胞嘧啶脱氨酶（AID）的表达。
结果
CBD 患儿和成人 PBM 患者的胆囊上皮细胞的 Ki-67 标记指数（LI）和 KRAS、p53、HDAC 和 AID 的表达均明显高于或有倾向于高于对照组。
结论
通过 HDAC 和 AID 表达以及表观遗传和遗传调控，CBD 患儿和成人 PBM 患者可能会在日后发生 BTC。
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