Histological diagnosis of polyploidy discriminates an aggressive subset of hepatocellular carcinomas with poor prognosis
Menée à partir de l'analyse histologique d'échantillons tumoraux prélevés sur 56 patients atteints d'un carcinome hépatocellulaire, cette étude identifie les caractéristiques des tumeurs polyploïdes ainsi que des marqueurs permettant de les identifier puis met en évidence une association entre la présence abondante de cellules géantes polyploïdes, la surexpression de l'enzyme de conjugaison à l'ubiquitine UBE2C et un pronostic défavorable
Background : 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.
Methods : 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.
Results : 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.
Conclusions : Histological diagnosis of polyploidy using surrogate markers discriminates an aggressive subset of HCC, apart from known HCC subgroups, and predict poor prognosis in HCC.
British Journal of Cancer , article en libre accès, 2023