Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002 Thailand.
Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002 Thailand; Cholangiocarcinoma Research Institute (CARI), Khon Kaen University, Khon Kaen, 40002 Thailand.
Hum Pathol. 2022 Aug;126:31-44. doi: 10.1016/j.humpath.2022.05.008. Epub 2022 May 13.
Cholangiocarcinoma (CCA) is a highly aggressive malignant tumor that has highest incidence in northeastern Thailand. The survival rate of CCA patients after receiving surgical treatment is quite low. Recently, genetic alterations including chromosome abnormalities have been studied as predictive factors and to aid planning for further treatment. This study aims to investigate the association between chromosomal aberrations, clinical data, and overall survival time of CCA patients. Formalin-fixed paraffin-embedded (FFPE) tissues from 194 CCA patients were examined. The copy numbers of chromosomes 3, 7, 17 and 9p21 were investigated using the UroVysion® fluorescence in-situ hybridization (FISH) assay. The overall survival time (OS) of CCA patients with or without polysomy of chromosomes 3, 7, 17 and/or loss of 9p21 were statistically analyzed in association with their clinicopathological parameters. Kaplan-Meier analysis was performed. The OS of patients with polysomy of chromosomes 3 + 7 was significantly shorter than those without this polysomy (log-rank P = 0.006; median OS 14.79 vs. 19.62 months). Moreover, patients with polysomy of chromosomes 3 + 7+17 and heterozygous for 9p21 loss have significantly shorter survival time than those without such chromosomal aberrations (log-rank P = 0.001; median OS 15.74 vs. 37.57 months). Interestingly, multivariate analysis revealed that polysomy of chromosomes 3 + 7 and of chromosomes 3 + 7+17 with 9p21 heterozygous loss were independent predictive factors of a poor OS (P = 0.027; P = 0.008, respectively).The chromosomal aberrations patterns which we evaluated using FISH; 1) polysomy of chromosomes 3 + 7 and 2) polysomy of chromosomes 3 + 7+17 with 9p21 heterozygous loss, have strong potential as indicators of poor prognosis in CCA patients.
胆管癌（CCA）是一种高度侵袭性的恶性肿瘤，在泰国东北部发病率最高。接受手术治疗的 CCA 患者的生存率相当低。最近，包括染色体异常在内的遗传改变已被研究作为预测因素，并有助于规划进一步的治疗。本研究旨在探讨染色体异常与 CCA 患者的临床数据和总生存时间之间的关系。对 194 例 CCA 患者的福尔马林固定石蜡包埋（FFPE）组织进行了检查。使用 UroVysion®荧光原位杂交（FISH）检测染色体 3、7、17 和 9p21 的拷贝数。统计分析了 CCA 患者染色体 3、7、17 三体和/或 9p21 缺失与临床病理参数的关系。进行 Kaplan-Meier 分析。染色体 3+7 三体的患者的总生存时间（OS）明显短于非三体的患者（对数秩 P=0.006；中位 OS 14.79 与 19.62 个月）。此外，染色体 3+7+17 三体和杂合性 9p21 缺失的患者的生存时间明显短于无此类染色体异常的患者（对数秩 P=0.001；中位 OS 15.74 与 37.57 个月）。有趣的是，多变量分析显示，染色体 3+7 三体和染色体 3+7+17 三体伴 9p21 杂合缺失是 OS 不良的独立预测因素（P=0.027；P=0.008）。我们使用 FISH 评估的染色体异常模式；1）染色体 3+7 三体，2）染色体 3+7+17 三体伴 9p21 杂合缺失，具有作为 CCA 患者预后不良的潜在指标的强大潜力。
