Objectives Polyploidy is a fascinating characteristic of liver parenchyma. Hepatocyte polyploidy depends on the DNA content of each nucleus (nuclear ploidy) and the number of nuclei per cell (cellular ploidy). Which role can be assigned to polyploidy during human hepatocellular carcinoma (HCC) development is still an open question. Here, we investigated whether a specific ploidy spectrum is associated with clinical and molecular features of HCC. Design Ploidy spectra were determined on surgically resected tissues from patients with HCC as well as healthy control tissues. To define ploidy profiles, a quantitative and qualitative in situ imaging approach was used on paraffin tissue liver sections. Results We first demonstrated that polyploid hepatocytes are the major components of human liver parenchyma, polyploidy being mainly cellular (binuclear hepatocytes). Across liver lobules, polyploid hepatocytes do not exhibit a specific zonation pattern. During liver tumorigenesis, cellular ploidy is drastically reduced; binuclear polyploid hepatocytes are barely present in HCC tumours. Remarkably, nuclear ploidy is specifically amplified in HCC tumours. In fact, nuclear ploidy is amplified in HCCs harbouring a low degree of differentiation and TP53 mutations. Finally, our results demonstrated that highly polyploid tumours are associated with a poor prognosis. Conclusions Our results underline the importance of quantification of cellular and nuclear ploidy spectra during HCC tumorigenesis.

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多倍体谱：HCC 分类的新标记

目的 多倍体是肝实质的一个迷人特征。肝细胞多倍性取决于每个细胞核的 DNA 含量（核倍性）和每个细胞的细胞核数量（细胞倍性）。在人类肝细胞癌 (HCC) 发展过程中，多倍体可以发挥何种作用仍然是一个悬而未决的问题。在这里，我们调查了特定倍性谱是否与 HCC 的临床和分子特征相关。设计倍性谱是对从 HCC 患者以及健康对照组织手术切除的组织确定的。为了定义倍性特征，在石蜡组织肝脏切片上使用了定量和定性的原位成像方法。结果我们首先证明了多倍体肝细胞是人肝实质的主要成分，多倍体主要是细胞（双核肝细胞）。在肝小叶中，多倍体肝细胞不表现出特定的分区模式。在肝脏肿瘤发生过程中，细胞倍性急剧减少；双核多倍体肝细胞几乎不存在于 HCC 肿瘤中。值得注意的是，核倍性在 HCC 肿瘤中被特异性放大。事实上，核倍性在具有低分化度和 TP53 突变的 HCC 中被放大。最后，我们的结果表明高度多倍体肿瘤与不良预后相关。结论我们的结果强调了在 HCC 肿瘤发生过程中量化细胞和核倍性谱的重要性。双核多倍体肝细胞几乎不存在于 HCC 肿瘤中。值得注意的是，核倍性在 HCC 肿瘤中被特异性放大。事实上，核倍性在具有低分化度和 TP53 突变的 HCC 中被放大。最后，我们的结果表明高度多倍体肿瘤与不良预后相关。结论我们的结果强调了在 HCC 肿瘤发生过程中量化细胞和核倍性谱的重要性。双核多倍体肝细胞几乎不存在于 HCC 肿瘤中。值得注意的是，核倍性在 HCC 肿瘤中被特异性放大。事实上，核倍性在具有低分化度和 TP53 突变的 HCC 中被放大。最后，我们的结果表明高度多倍体肿瘤与不良预后相关。结论我们的结果强调了在 HCC 肿瘤发生过程中量化细胞和核倍性谱的重要性。