Aneuploidy related transcriptional changes in endometrial cancer link low expression of chromosome 15q genes to poor survival

Mauland, Karen Klepsland; Wik, Elisabeth; Høivik, Erling A.; Kusonmano, Kanthida; Halle, Mari K.; Berg, Ansgar; Haugland, Hans Kristian; Øyan, Anne Margrete; Kalland, Karl‐Henning; Stefansson, Ingunn M.; Akslen, Lars A.; Krakstad, Camilla; Trovik, Jone; Werner, Henrica M.J.; Salvesen, Helga B.

doi:10.18632/oncotarget.14201

Cited by 6 publications

(2 citation statements)

References 59 publications

(77 reference statements)

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“…So at present some uncertainty surrounds the status of ER/PR in relation to ploidy and SPF. But a recent report has stated that aneuploidy is seen also in ER/PR negative endometrial tumours, where aneuploidy independently predicted survival (Mauland et al 2017). One has to be mindful of considering the expression status of ER and PR and be circumspect about this since they would have opposing biological effects; so do the ER isoforms biologically oppose each other.…”

Section: The Connotation Of Er and Pr On Dna Ploidy Spf And Cell Cycmentioning

confidence: 99%

Does DNA ploidy and synthesis phase dynamic accentuate the predictive power of oestrogen and progesterone receptors in breast cancer progression and prognosis?

Sherbet¹,

Dlay²

2018

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Oestrogen and progesterone receptors (ER and PR) are closely associated with breast cancer progression. In this review we identify and discuss cellular markers that can accentuate or complement the deployment of ER and PR for predicting prognosis. The focus is on aneuploidy and DNA ploidy which appear to be significant independent predictors of overall survival in many forms of cancer. Their importance in cancer development and progression flows from their origin in the inherent genetic instability. Genetic instability of chromosomes is seen as aneuploidy, chromosomal deletions, translocations and sister-chromatid recombination, and at the DNA level as altered DNA repair, gene amplification and deletion and point mutations. Microsatellite loci of repetitive nucleotide sequences are inherently unstable. Microsatellite instability is characterised by the loss of DNA mismatch repair activity leading to a hypermutable phenotype. Chromosome abnormalities result from the deregulation of cell cycle and immune checkpoint regulators. Failure of Oestrogen and progesterone receptors in breast cancer

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Section: The Connotation Of Er and Pr On Dna Ploidy Spf And Cell Cycmentioning

confidence: 99%

Does DNA ploidy and synthesis phase dynamic accentuate the predictive power of oestrogen and progesterone receptors in breast cancer progression and prognosis?

Sherbet¹,

Dlay²

2018

Atlas of Genetics and Cytogenetics in Oncology and Haematology

View full text Add to dashboard Cite

show abstract

“…Patient series selected for the analysis of protein expression by IHC using FFPE tissues of cancers prepared on TMAs, as well as data and for tumor ploidy as assessed by flow cytometry, have been described earlier (1,2,(7)(8)(9)(10).…”

mentioning

confidence: 99%

Supplementary Methods from <i>PIK3CA</i> Amplification Associates with Aggressive Phenotype but Not Markers of AKT-MTOR Signaling in Endometrial Carcinoma

Holst¹,

Werner²,

Mjos³

et al. 2023

Preprint

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Combination of aneuploidy and high S-phase fraction indicates increased risk of relapse in stage I endometrioid endometrial carcinoma

et al. 2021

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Introduction: Endometrioid endometrial carcinoma is a cancer type with generally excellent prognosis when diagnosed at an early stage, but there is a subset of patients with relapsing disease in spite of early diagnosis and surgical treatment. There is a need to find prognostic markers to identify these patients with increased risk of relapse. Depth of myometrial invasion, histological grade, and presence of lymphovascular invasion are known risk factors. DNA content (ploidy) and proliferation measured as S-phase fraction (SPF) have been discussed as prognostic markers but need additional evaluation. Material and methods: We evaluated relapse-free survival (RFS) with respect to ploidy and SPF, which was analyzed by flow cytometry on fresh tumor tissue, in a cohort of 1001 women treated for stage I endometrioid endometrial carcinoma in northern Sweden during the period of 1993-2010, with a median follow up time of 12.0 years. Data were obtained from historical records. Results: In simple analysis, both aneuploidy and high SPF were associated to increased risk of relapse with hazard ratios (HR) 2.37 (95% CI 1.52-3.70) and 1.94 (95% CI 1.24-3.02), respectively. Our data also confirmed stage, tumor grade, and ploidy as independent prognostic markers in an age adjusted cox regression multivariable analysis but we did not find SPF to contribute to prognosis. However, the combination of aneuploidy and high SPF identified a group of patients with increased risk of relapse, HR 2.02 (95% CI 1. 19-3.44). Conclusion:In this study, which is the largest study of ploidy and SPF in stage I endometrioid endometrial carcinoma using fresh frozen tissue, aneuploidy was shown to be an independent prognostic marker. Furthermore, the combination of aneuploidy and high SPF could be used to identify patients with increased risk of relapse.

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Aneuploidy related transcriptional changes in endometrial cancer link low expression of chromosome 15q genes to poor survival

Cited by 6 publications

References 59 publications

Does DNA ploidy and synthesis phase dynamic accentuate the predictive power of oestrogen and progesterone receptors in breast cancer progression and prognosis?

Does DNA ploidy and synthesis phase dynamic accentuate the predictive power of oestrogen and progesterone receptors in breast cancer progression and prognosis?

Supplementary Methods from <i>PIK3CA</i> Amplification Associates with Aggressive Phenotype but Not Markers of AKT-MTOR Signaling in Endometrial Carcinoma

Combination of aneuploidy and high S-phase fraction indicates increased risk of relapse in stage I endometrioid endometrial carcinoma

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