Assessment of DNA Ploidy in the ProMisE molecular subgroups of endometrial cancer

Gynecol Oncol. 2017 Sep;146(3):596-602. doi: 10.1016/j.ygyno.2017.06.020. Epub 2017 Jun 21.

Abstract

Objective: We sought to determine whether DNA ploidy correlates with the four molecular subgroups of endometrial carcinoma (EC) as determined using ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer).

Methods: 90 cases of EC previously characterized by clinicopathological parameters, outcomes, and ProMisE molecular subgroup (POLE EDM, MMR-D, p53 wt or p53 abn) were assessed for DNA ploidy using image cytometry. Associations of ploidy with traditional clinicopathological parameters were also tested.

Results: Abnormal DNA ploidy status differed amongst the ProMisE groups (p<0.001) and was found in 80.9% (17/21) of p53 abn, 37.0% (10/27) of p53 wt, 28.6% (4/14) of POLE EDM and 14.3% (4/28) of MMR-D. Abnormal DNA content was significantly associated with lower BMI (p=0.034) and grade 3 tumors (p=0.001). In the entire cohort, abnormal DNA content was significantly associated with worse progression free survival (p=0.0094) but not disease specific survival (p=0.249) or overall survival (p=0.187). When examining ploidy within each of the ProMisE groups, abnormal DNA content correlated with worse overall survival (p=0.041) and progression free survival (p=0.011) in the MMR-D group. No statistically significant relationship was seen in the remaining 3 groups.

Conclusion: Abnormal DNA ploidy status did correlate with the molecular subgroups of EC; abnormal DNA content was seen in the large majority of p53 abn cases. Abnormal ploidy however was also seen in smaller numbers in the p53 wt, POLE EDM and MMR-D groups; therefore abnormal DNA content was not a specific marker for any one molecular group. The addition of ploidy to the ProMisE molecular categories conferred additional prognostic value within the MMR-D group, which merits further study.

Keywords: Aneuploidy; DNA ploidy; Endometrial carcinoma; Image cytometry; Molecular; TCGA; The Cancer Genome Atlas.

MeSH terms

  • Aged
  • Aneuploidy
  • Carcinoma / chemistry
  • Carcinoma / genetics*
  • Carcinoma / pathology*
  • DNA Mismatch Repair / genetics
  • DNA Polymerase II / genetics
  • DNA, Neoplasm / genetics*
  • Diploidy
  • Disease-Free Survival
  • Endometrial Neoplasms / chemistry
  • Endometrial Neoplasms / genetics*
  • Endometrial Neoplasms / pathology*
  • Female
  • Humans
  • Middle Aged
  • Mutation
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Ploidies*
  • Poly-ADP-Ribose Binding Proteins
  • Receptors, Estradiol / analysis
  • Receptors, Progesterone / analysis
  • Survival Rate
  • Tetraploidy
  • Tumor Suppressor Protein p53 / genetics

Substances

  • DNA, Neoplasm
  • Poly-ADP-Ribose Binding Proteins
  • Receptors, Estradiol
  • Receptors, Progesterone
  • Tumor Suppressor Protein p53
  • DNA Polymerase II
  • POLE protein, human