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Aims: To determine the frequency and survival of the various types of uterine sarcoma in the total population of Norway and evaluate histopathological prognostic factors in order to identify risk groups. Methods and results: Histopathological review of all uterine sarcoma cases reported to the Norwegian Cancer Registry during 1970–2000 was undertaken. Survival dates were provided by The Cancer Registry. Kaplan–Meier survival curves were generated. The log rank test was used for univariate analysis and a Cox proportional hazards regression model for multivariate evaluation of survival. Stage of disease was the most important prognostic factor for all tumour types. Tumour size and the mitotic index (MI) were significant prognostic factors ( P < 0.0001) in leiomyosarcomas confined to the uterus and allowed for separation into three risk groups with marked differences in prognosis. The prognosis of endometrial stromal sarcomas confined to the uterus was related to MI ( P < 0.0001) and tumour cell necrosis ( P < 0.004). Combining these parameters allowed for separation into three risk groups with marked difference in prognosis. In adenosarcomas, tumour cell necrosis was the only significant prognostic factor. Conclusions: There are marked differences in survival between uterine sarcoma types. Leiomyosarcomas and endometrial stromal sarcomas can be divided into different groups. [ABSTRACT FROM AUTHOR]

Background: Nuclear texture analysis is a useful method to obtain quantitative information for use in prognosis of cancer. The first-order gray level statistics of a digitized light microscopic nuclear image may be influenced by variations in the image input conditions. Therefore, we have previously standardized the nuclear gray level mean value and standard deviation. However, there is a clear relation between nuclear DNA content, area, first-order statistics, and texture. For nuclei with approximately the same DNA content, the mean gray level increases with an increasing nuclear area. The aims of the present methodical work were to study: (1) whether the prognostic value of adaptive textural features varies with nuclear area, and (2) the effect of standardizing nuclear first-order statistics. Methods: Nuclei from 134 cases of ovarian cancer were grouped into intervals according to nuclear area. Adaptive features were extracted from two different image sets, i.e., standardized and non-standardized nuclear images. Results: The prognostic value of adaptive textural features varied strongly with nuclear area. A standardization of the first-order statistics significantly reduced this prognostic information. Several single features discriminated the two classes of cancer with a correct classification rate of 70%. Conclusion: Nuclei having an area between 2000–4999 pixels contained most of the class distance information between the good and poor prognosis classes of cancer. By considering the relation between nuclear area and texture, we avoided a loss of information caused by standardizing the first-order statistics and mixing data from cells having different nuclear area. [ABSTRACT FROM AUTHOR]

Simple Summary: Chromatin organisation affects gene expression and contributes to carcinogenesis. Automatic quantification of chromatin heterogeneity can be applied to identify patients with increased risk of cancer recurrence and death in several cancer types. We aimed to investigate the prognostic role of diversity of chromatin compartments in relation to chromatin heterogeneity and as a potential supplement to pathological risk classifications in gynaecological carcinomas. To this end, we computed the entropy of both chromatin compartment sizes and optical densities within compartments. In analysis of two cohorts consisting of 1037 patients with gynaecological carcinoma, we observed a moderately strong correlation between the prognostic value of the entropies and chromatin heterogeneity. The entropies provided an objective marker, which, integrated with pathological risk classifications, might possibly contribute to the selection of high-risk stage I ovarian carcinoma patients for adjuvant chemotherapy and to preoperative identification of low-risk endometrial carcinoma patients who are candidates for less extensive surgery. Statistical texture analysis of cancer cell nuclei stained for DNA has recently been used to develop a pan-cancer prognostic marker of chromatin heterogeneity. In this study, we instead analysed chromatin organisation by automatically quantifying the diversity of chromatin compartments in cancer cell nuclei. The aim was to investigate the prognostic value of such an assessment in relation to chromatin heterogeneity and as a potential supplement to pathological risk classifications in gynaecological carcinomas. The diversity was quantified by calculating the entropy of both chromatin compartment sizes and optical densities within compartments. We analysed a median of 281 nuclei (interquartile range (IQR), 273 to 289) from 246 ovarian carcinoma patients and a median of 997 nuclei (IQR, 502 to 1452) from 791 endometrial carcinoma patients. The prognostic value of the entropies and chromatin heterogeneity was moderately strongly correlated (r ranged from 0.68 to 0.73), but the novel marker was observed to provide additional prognostic information. In multivariable analysis with clinical and pathological markers, the hazard ratio associated with the novel marker was 2.1 (95% CI, 1.3 to 3.5) in ovarian carcinoma and 2.4 (95% CI, 1.5 to 3.9) in endometrial carcinoma. Integration with pathological risk classifications gave three risk groups with distinctly different prognoses. This suggests that the novel marker of diversity of chromatin compartments might possibly contribute to the selection of high-risk stage I ovarian carcinoma patients for adjuvant chemotherapy and low-risk endometrial carcinoma patients for less extensive surgery. [ABSTRACT FROM AUTHOR]

Background: Chromatin organisation affects gene expression and regional mutation frequencies and contributes to carcinogenesis. Aberrant organisation of DNA has been correlated with cancer prognosis in analyses of the chromatin component of tumour cell nuclei using image texture analysis. As yet, the methodology has not been sufficiently validated to permit its clinical application. We aimed to define and validate a novel prognostic biomarker for the automatic detection of heterogeneous chromatin organisation.Methods: Machine learning algorithms analysed the chromatin organisation in 461 000 images of tumour cell nuclei stained for DNA from 390 patients (discovery cohort) treated for stage I or II colorectal cancer at the Aker University Hospital (Oslo, Norway). The resulting marker of chromatin heterogeneity, termed Nucleotyping, was subsequently independently validated in six patient cohorts: 442 patients with stage I or II colorectal cancer in the Gloucester Colorectal Cancer Study (UK); 391 patients with stage II colorectal cancer in the QUASAR 2 trial; 246 patients with stage I ovarian carcinoma; 354 patients with uterine sarcoma; 307 patients with prostate carcinoma; and 791 patients with endometrial carcinoma. The primary outcome was cancer-specific survival.Findings: In all patient cohorts, patients with chromatin heterogeneous tumours had worse cancer-specific survival than patients with chromatin homogeneous tumours (univariable analysis hazard ratio [HR] 1·7, 95% CI 1·2-2·5, in the discovery cohort; 1·8, 1·0-3·0, in the Gloucester validation cohort; 2·2, 1·1-4·5, in the QUASAR 2 validation cohort; 3·1, 1·9-5·0, in the ovarian carcinoma cohort; 2·5, 1·8-3·4, in the uterine sarcoma cohort; 2·3, 1·2-4·6, in the prostate carcinoma cohort; and 4·3, 2·8-6·8, in the endometrial carcinoma cohort). After adjusting for established prognostic patient characteristics in multivariable analyses, Nucleotyping was prognostic in all cohorts except for the prostate carcinoma cohort (HR 1·7, 95% CI 1·1-2·5, in the discovery cohort; 1·9, 1·1-3·2, in the Gloucester validation cohort; 2·6, 1·2-5·6, in the QUASAR 2 cohort; 1·8, 1·1-3·0, for ovarian carcinoma; 1·6, 1·0-2·4, for uterine sarcoma; 1·43, 0·68-2·99, for prostate carcinoma; and 1·9, 1·1-3·1, for endometrial carcinoma). Chromatin heterogeneity was a significant predictor of cancer-specific survival in microsatellite unstable (HR 2·9, 95% CI 1·0-8·4) and microsatellite stable (1·8, 1·2-2·7) stage II colorectal cancer, but microsatellite instability was not a significant predictor of outcome in chromatin homogeneous (1·3, 0·7-2·4) or chromatin heterogeneous (0·8, 0·3-2·0) stage II colorectal cancer.Interpretation: The consistent prognostic prediction of Nucleotyping in different biological and technical circumstances suggests that the marker of chromatin heterogeneity can be reliably assessed in routine clinical practice and could be used to objectively assist decision making in a range of clinical settings. An immediate application would be to identify high-risk patients with stage II colorectal cancer who might have greater absolute benefit from adjuvant chemotherapy. Clinical trials are warranted to evaluate the survival benefit and cost-effectiveness of using Nucleotyping to guide treatment decisions in multiple clinical settings.Funding: The Research Council of Norway, the South-Eastern Norway Regional Health Authority, the National Institute for Health Research, and the Wellcome Trust. [ABSTRACT FROM AUTHOR]