虽然认为基因组复制，或多倍化，被认为是推动癌症进化和影响肿瘤特征的因素，但它在肝细胞癌（HCC）中的意义尚不清楚。我们旨在通过评估染色体复制来确定多倍体HCC的特征，并探索代表多倍体HCC的替代标记。通过多染色体的荧光原位杂交，评估了人类HCC中的倍性。比较了多倍体和近二倍体HCC之间的临床病理学和表达特征。通过对培养的HCC细胞的转录组分析，探索了表示多倍体HCC的标志物。发现36%（20/56）的HCC中存在多倍体，并且与近二倍体HCC相比，多倍体HCC有高血清甲胎蛋白，差异化程度较差和预后较差的特点，显示出一种侵袭性亚组。分子分类显示多倍体HCC高度表达甲胎蛋白，但不一定具有祖细胞特征。组织学检查显示多倍体HCC中含有大量的多倍体巨噬细胞（PGCCs），具有独特的外观和频繁的大髓束-大量结构。值得注意的是，多倍体HCC中PGCCs的丰度和泛素连接酶2C的过表达表明多倍化在HCC中，并能有效预测预后不良。通过使用替代标志物进行组织学诊断，将侵袭性HCC亚组与已知HCC亚组区分开来，并预测HCC的预后不良。©2023年。作者。

Although genome duplication, or polyploidization, is believed to drive cancer evolution and affect tumor features, its significance in hepatocellular carcinoma (HCC) is unclear. We aimed to determine the characteristics of polyploid HCCs by evaluating chromosome duplication and to discover surrogate markers to discriminate polyploid HCCs.The ploidy in human HCC was assessed by fluorescence in situ hybridization for multiple chromosomes. Clinicopathological and expression features were compared between polyploid and near-diploid HCCs. Markers indicating polyploid HCC were explored by transcriptome analysis of cultured HCC cells.Polyploidy was detected in 36% (20/56) of HCCs and discriminated an aggressive subset of HCC that typically showed high serum alpha-fetoprotein, poor differentiation, and poor prognosis compared to near-diploid HCCs. Molecular subtyping revealed that polyploid HCCs highly expressed alpha-fetoprotein but did not necessarily show progenitor features. Histological examination revealed abundant polyploid giant cancer cells (PGCCs) with a distinct appearance and frequent macrotrabecular-massive architecture in polyploid HCCs. Notably, the abundance of PGCCs and overexpression of ubiquitin-conjugating enzymes 2C indicated polyploidy in HCC and efficiently predicted poor prognosis in combination.Histological diagnosis of polyploidy using surrogate markers discriminates an aggressive subset of HCC, apart from known HCC subgroups, and predict poor prognosis in HCC.© 2023. The Author(s).