CANCER-RELATED GENETIC CHANGES IN MULTISTEP HEPATOCARCINOGENESIS AND THEIR CORRELATION WITH IMAGING AND HISTOLOGICAL FINDINGS.

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 ofhTERT. 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 werehTERT(61.5%), followed byTP53(42.7%),RB1(24.8%), andCTNNB1(18.8%). Liver tumors were classified into six imaging groups/grades, and the prevalence ofhTERTmutations tended to increase with the advancement of imaging/histological grades (P = 0.026 and 0.13, respectively), whereas no such tendency was evident forTP53mutation (P = 0.78 and 1.00, respectively). Focusing on the mutations in each tumor, although the variant frequency (VF) ofhTERTdid not change (P = 0.36 and 0.14, respectively) in association with imaging/histological grades,TP53VF increased significantly (P = 0.004 and <0.001, respectively). In multivariate analysis, stage III or IV (hazard ratio, 3.64;P = 0.003),TP53VF >= 50% (hazard ratio, 3.79;P = 0.020) was extracted as an independent risk for recurrence in primary HCC patients. Conclusions Increased prevalence ofhTERTmutation and increasedTP53mutation VF are characteristic features of HCC progression, diagnosed with imaging/histological studies.