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Cancer‐related genetic changes in multistep hepatocarcinogenesis and their correlation with imaging and histological findings
Author(s) -
Muraoka Masaru,
Maekawa Shinya,
Suzuki Yuichiro,
Sato Mitsuaki,
Tatsumi Akihisa,
Matsuda Shuya,
Miura Mika,
Nakakuki Natsuko,
Shindo Hiroko,
Amemiya Fumitake,
Takano Shinichi,
Fukasawa Mitsuharu,
Nakayama Yasuhiro,
Yamaguchi Tatsuya,
Inoue Taisuke,
Sato Tadashi,
Yamashita Atsuya,
Moriishi Kohji,
Matsuda Masanori,
Enomoto Nobuyuki
Publication year - 2020
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/hepr.13529
Subject(s) - telomerase reverse transcriptase , magnetic resonance imaging , hepatocellular carcinoma , medicine , hazard ratio , pathology , nuclear medicine , biology , radiology , gene , telomerase , genetics , confidence interval
Aim The landscape of cancer‐related genetic aberrations in hepatocellular carcinoma (HCC) has gradually become clear through recent next‐generation sequencing studies. However, it remains unclear how genetic aberrations correlate with imaging and histological findings. Methods Using 117 formalin‐fixed paraffin‐embedded specimens of primary liver tumors, we undertook targeted next‐generation sequencing of 50 cancer‐related genes and digital polymerase chain reaction of hTERT . After classifying tumors into several imaging groups by hierarchal clustering with the information from gadoxetic acid enhanced magnetic resonance imaging, contrast‐enhanced computed tomography, contrast‐enhanced ultrasound, and diffusion‐weighted imaging magnetic resonance imaging, the correlation between genetic aberrations and imaging and histology were investigated. Results Most frequent mutations were hTERT (61.5%), followed by TP53 (42.7%), RB1 (24.8%), and CTNNB1 (18.8%). Liver tumors were classified into six imaging groups/grades, and the prevalence of hTERT mutations tended to increase with the advancement of imaging/histological grades ( P = 0.026 and 0.13, respectively), whereas no such tendency was evident for TP53 mutation ( P = 0.78 and 1.00, respectively). Focusing on the mutations in each tumor, although the variant frequency (VF) of hTERT did not change ( P = 0.36 and 0.14, respectively) in association with imaging/histological grades, TP53 VF increased significantly ( P = 0.004 and <0.001, respectively). In multivariate analysis, stage III or IV (hazard ratio, 3.64; P = 0.003), TP53 VF ≥ 50% (hazard ratio, 3.79; P = 0.020) was extracted as an independent risk for recurrence in primary HCC patients. Conclusions Increased prevalence of hTERT mutation and increased TP53 mutation VF are characteristic features of HCC progression, diagnosed with imaging/histological studies.