Proportion of Cancer Cell Nuclei With High Chromatin Entropy and Outcome in Gynecologic Cancers


Key Points

  • A higher proportion of high chromatin entropy nuclei was associated with poorer outcome in gynecologic cancers.
  • The biomarker was independently associated with poorer overall survival in uterine sarcoma, higher recurrence rate in ovarian cancer, and poorer cancer-specific survival in endometrial cancer.  

In a study reported in the Journal of the National Cancer Institute, Nielsen et al found significant associations between higher proportions of cancer cell nuclei with high chromatin entropy (associated with genomic instability) and poorer outcomes in gynecologic cancers.

Study Details

In the study, a novel texture-based biomarker characterizing individual cancers based on proportion of high–chromatin entropy nuclei (< 25% vs ≥ 25%) using high-resolution digital imaging for cell-by-cell chromatin analysis was developed in a discovery cohort of 175 uterine sarcomas. The prognostic ability of the biomarker was assessed in validation sets of 179 uterine sarcomas, 246 early-stage ovarian carcinomas, and 791 endometrial carcinomas, with more than 1 million images of nuclei stained for DNA being included in the study.

Prognostic Ability

A higher proportion (≥ 25%) of high–chromatin entropy nuclei was associated with poorer 5-year overall survival among patients with uterine sarcoma (28.1% vs 56.5%, hazard ratio [HR] = 2.02, 95% confidence interval [CI] = 1.43–2.84), time to recurrence among patients with ovarian cancer (10-year recurrence = 55.6% vs 24.9%, HR = 2.91, 95% CI = 1.74–4.88), and 5-year cancer-specific survival among patients with endometrial cancer (65.8% vs 87.5%, HR = 3.74, 95% CI = 2.24–6.24). In multivariate analysis including clinicopathologic parameters, higher chromatin entropy was an independent prognostic marker for 5-year overall survival in uterine sarcoma (HR = 1.81, 95% CI = 1.21–2.70), time to recurrence in ovarian cancer (HR = 1.71, 95% CI = 1.01–2.90), and 5-year cancer-specific survival in endometrial cancer (HR = 2.03, 95% CI = 1.19–3.45).

The investigators concluded, “A novel method detected high–chromatin entropy nuclei, and an increased proportion of such nuclei was associated with poor prognosis. Chromatin entropy supplemented existing prognostic markers in multivariable analyses of three gynecological cancer cohorts.”

The study was supported by the Research Council of Norway and South-Eastern Norway Regional Health Authority.

Håvard Emil Danielsen, PhD, of the Institute for Cancer Genetics and Informatics, Oslo University Hospital, is the corresponding author for the Journal of the National Cancer Institute article. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.