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Biomarker predicts prognosis in certain gynecological cancers

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June 1, 2018

Researchers identified chromatin entropy nuclei as a prognostic marker for patients with uterine sarcomas, ovarian carcinomas and endometrial carcinomas, according to published findings.

High-chromatin entropy nuclei — identified using nuclear texture analysis — appeared associated with poor prognosis.

Nuclear texture analysis, also known as nucleotyping, has been used to identify prognostic biomarkers in various cancers. The analysis characterizes changes in chromatin structure in cancer nuclei through measuring pixel gray levels in subregions of nuclear images. Entropy can be used to appraise heterogeneity in the chromatin and act as a prognostic marker in several gynecological cancers.

“The aim of the present study was to test the hypotheses that there exists a subpopulation of cells with high chromatin entropy and that there is an association between the presence of such cell nuclei and clinical outcomes,” Birgitte Nielsen, PhD, researcher at Institute for Cancer Genetics and Informatics at Oslo University Hospital in Norway, and colleagues wrote.

Investigators developed and evaluated a nucleotyping biomarker for 587 uterine sarcomas — which were divided into discovery (n = 175) and validation (n = 179) datasets — 246 ovarian carcinomas and 1,046 endometrial carcinomas. Researchers further divided patients from the discovery set into a good prognosis class or poor prognosis class.

The biomarker — developed using only nuclei sized between 54µm2 and 134µm2 — was used to characterize each cancer based on the number of high-chromatin entropy nuclei in the discovery set of uterine sarcomas.

The prognostic impact was then measured on a validation set of uterine sarcomas and independent validation sets of early-stage ovarian carcinomas and endometrial carcinomas.

Researchers stained more than 1 million images of nuclei for DNA.

In the discovery set, 5-year OS was 27.6% (95% CI, 13.1-44.3) for high chromatin entropy patients compared with 57.5% (95% CI, 49.1-65.1) for patients with low chromatin entropy (HR = 2.13; 95% CI, 1.3-3.49).

In the sarcoma validation set, researchers observed a significant difference in survival between patients with high chromatin entropy (28.1%; 95% CI, 14-44.1) and low chromatin entropy (56.5%; 95% CI, 48.1-64), for an HR of 1.91 (95% CI, 1.18-3.08).

The 5-year OS for all uterine sarcoma patients was 57% (95% CI, 51.1-62.4) for low chromatin entropy and 27.9% (95% CI, 17.3-39.4) for high chromatin entropy, for an HR of 2.02 (95% CI, 1.43-2.84).

The recurrence rate for ovarian cancer was 55.6% (95% CI, 40.4-72) among high-chromatin entropy patients compared with 24.9% (95% CI, 19.6-31.4) among low-chromatin entropy patients (HR = 2.91; 95% CI, 1.74-4.88).

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Multivariate analysis with histologic grade and Federation of Gynecology and Obstetrics stage showed chromatin entropy was an independent prognostic marker (HR = 1.71; 95% CI, 1.01-2.9).

In the endometrial cancer validation set, 5-year cancer-specific survival was 65.8% (95% CI, 51.3-77) for patients with high-chromatin entropy tumors compared with 87.5% (95% CI, 83.8-90.4) for patients with low-chromatin entropy tumors (HR = 3.74; 95% CI, 2.24-6.24).

Multivariate analysis that included age and curettage histology showed chromatin entropy to be an independent prognostic marker (HR = 2.03; 95% CI, 1.19-3.45).

“Chromatin entropy offered prognostic information in patients defined as high risk by stage and grade and could thus possibly aid in selecting patients who could be treated with single-agent carboplatin and patients who could be candidates for more aggressive combination chemotherapy,” the researchers wrote. “Chromatin entropy could also possibly be used to select low-risk patients who should be considered for adjuvant chemotherapy, but this remains uncertain because our data did not allow reliable evaluation in this subgroup.” – by Melinda Stevens

Disclosure s : The Research Council of Norway supported this research. The authors report no relevant financial disclosures.

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