Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospita; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China.
Affiliated Hospital of Weifang Medical University, Weifang, 261031, China.
BMC Cancer. 2020 Apr 15;20(1):318. doi: 10.1186/s12885-020-06804-6.
Isocitrate dehydrogenase 1/2 (IDH1/2), BAP1, ARID1A and PBRM1 have been reported as the most frequent mutant genes in intrahepatic cholangiocarcinoma (ICC), and their relationships with clinicopathological features and prognosis were researched in this study.
We collected clinical data of 130 ICC patients from January 2012 to December 2017. The IDH1/2 mutation and loss of BAP1, ARID1A and PBRM1 expressions were detected by DNA sequencing or immunohistochemical methods, and histological subtype of ICCs was determined by hematoxylin-eosin, Alcian blue and S100P staining.
IDH1/2 mutation was related to decreased preoperative serum total bilirubin (P = 0.039), ferritin (P = 0.000) and higher histological differentiation (P = 0.024), and was associated with prolonged disease-free survival (P = 0.009) and a trend toward increased overall survival (P = 0.126) in small duct type of ICCs. Immunohistochemical staining results of MsMab-1 were generally consistent with DNA sequencing for IDH1/2 mutant in ICCs (κ = 0.691). Only BAP1 expression loss was correlated to prolonged disease-free survival (P = 0.031) and overall survival (P = 0.041) in large duct type of ICCs.
IDH1/2 mutation is a favorable predictor and may be related to iron metabolism in small duct type of ICCs. Furthermore, we suggest that the detection of IDH1/2 mutation is indispensable to determine targeted therapy in small duct type ICCs, while it is not necessary in large duct of ICCs. MsMab-1 is a relatively effective multi-specific antibody against IDH1/2 mutant in ICCs. BAP1 expression loss was correlated with improved prognosis only in large duct type ICCs.
异柠檬酸脱氢酶 1/2（IDH1/2）、BAP1、ARID1A 和 PBRM1 已被报道为肝内胆管癌（ICC）中最常见的突变基因，本研究探讨了它们与临床病理特征和预后的关系。
我们收集了 2012 年 1 月至 2017 年 12 月期间 130 例 ICC 患者的临床资料。通过 DNA 测序或免疫组织化学方法检测 IDH1/2 突变和 BAP1、ARID1A 和 PBRM1 的表达缺失，并通过苏木精-伊红、阿尔辛蓝和 S100P 染色确定 ICC 的组织学亚型。
IDH1/2 突变与术前血清总胆红素（P=0.039）、铁蛋白（P=0.000）降低和组织学分化程度较高（P=0.024）有关，与小胆管型 ICC 的无病生存时间延长（P=0.009）和总生存时间延长（P=0.126）有关。ICC 中 MsMab-1 的免疫组化染色结果与 IDH1/2 突变的 DNA 测序结果基本一致（κ=0.691）。仅 BAP1 表达缺失与大胆管型 ICC 的无病生存时间（P=0.031）和总生存时间（P=0.041）延长有关。
IDH1/2 突变是一个有利的预测因子，可能与小胆管型 ICC 的铁代谢有关。此外，我们建议在小胆管型 ICC 中检测 IDH1/2 突变对于确定靶向治疗是必不可少的，而在大胆管型 ICC 中则没有必要。MsMab-1 是一种针对 ICC 中 IDH1/2 突变体的相对有效的多特异性抗体。BAP1 表达缺失仅与大胆管型 ICC 的预后改善有关。
