https://scholars.lib.ntu.edu.tw/handle/123456789/589568
標題: | Lymphoepithelioma-like Intrahepatic Cholangiocarcinoma Is a Distinct Entity With Frequent pTERT/TP53 Mutations and Comprises 2 Subgroups Based on Epstein-Barr Virus Infection | 作者: | JIA-HUEI TSAI JAU-YU LIAU Lee, Chia-Hsiang YUNG-MING JENG |
關鍵字: | cholangiocarcinoma | Epstein-Barr virus | immune checkpoint inhibitor | lymphoepithelioma-like carcinoma | PD-L1;cholangiocarcinoma; Epstein-Barr virus; immune checkpoint inhibitor; lymphoepithelioma-like carcinoma; PD-L1 | 公開日期: | 2021 | 卷: | 45 | 期: | 10 | 來源出版物: | The American journal of surgical pathology | 摘要: | The molecular characteristics of lymphoepithelioma-like intrahepatic cholangiocarcinoma (LELCC) remain elusive. We examined 27 LELCC cases through next-generation sequencing using a panel of genes commonly mutated in primary liver cancers. Alterations in BAP1, ARID1A, ARID2, and PBRM1 were detected through immunohistochemistry. Fluorescence in situ hybridization was performed to analyze FGFR2 fusions and CCND1 amplification. LELCC is histologically classified as predominantly undifferentiated or glandular. Epstein-Barr virus-encoded small RNA (EBER) expression was found in 16 LELCCs. Approximately 50% of LELCCs expressed programmed death-ligand 1 strongly. Notably, recurrent pTERT and TP53 mutations were detected in 9 (38%) and 8 (33%) tumors, respectively. Only 2 LELCCs exhibited loss of expression for PBRM1. Alterations in genes typically involved in intrahepatic cholangiocarcinoma, including IDH1, IDH2, ARID1A, ARID2, and BAP1, and FGFR2 fusions, were not identified. The 2-step clustering analysis showed 2 distinct subgroups in LELCC, which were separated by EBER expression. A meta-analysis of all reported cases (n=85) has shown that EBER+ LELCC is strongly associated with the female sex, younger age, and exhibited predominantly glandular differentiation (P=0.001, 0.012, and <0.001, respectively). Patients with EBER- LELCC were more likely to have viral hepatitis and cirrhosis (P=0.003 and 0.005, respectively). Genetic analysis demonstrated that EBER- LELCC was significantly associated with pTERT and TP53 mutations (P=0.033 and 0.008, respectively). In conclusion, LELCC is genetically distinct from intrahepatic cholangiocarcinoma. EBER- LELCC may exhibit a different pathogenesis from EBER+ LELCC. High programmed death-ligand 1 expression in LELCC has implications for potential immunotherapeutic strategies. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/589568 | ISSN: | 01475185 | DOI: | 10.1097/PAS.0000000000001716 | SDG/關鍵字: | arid2 protein; bap1 protein; CA 19-9 antigen; DNA mismatch repair protein MSH2; fibroblast growth factor receptor 2; mismatch repair protein PMS2; MutL protein homolog 1; pbrm1 protein; programmed death 1 ligand 1; protein; protein MSH6; protein p53; reti |
顯示於: | 病理學科所 |
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