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The prognostic value of molecular biomarkers, microsatellite instability, DNA ploidy and morphometric mean shortest nuclear axis in endometrial cancer is conflicting, possibly due to the fact that different studies have used mixtures of histotypes, FIGO stages and different non-standardized non-automated methods. We have evaluated the prognostic value of classical prognostic factors, molecular biomarkers, microsatellite instability, DNA ploidy and morphometric mean shortest nuclear axis in a population-based cohort of FIGO stage I endometrial endometrioid adenocarcinomas. Curettings of 224 FIGO stage I endometrial endometrioid adenocarcinoma patients were reviewed. Clinical information, including follow-up, was obtained from the patients' charts. Microsatellite instability and morphometric mean shortest nuclear axis were obtained in whole tissue sections and molecular biomarkers using tissue microarrays. DNA ploidy was analyzed by image cytometry. Univariate (Kaplan-Meier method) and multivariate (Cox model) survival analysis was performed. With median follow-up of 66 months (1-209), 14 (6%) patients developed metastases. Age, microsatellite instability, molecular biomarkers (p16, p21, p27, p53 and survivin) and morphometric mean shortest nuclear axis had prognostic value. With multivariate analysis, combined survivin, p21 and microsatellite instability overshadowed all other variables. Patients in which any of these features had favorable values had an excellent prognosis, in contrast to those with either high survivin or low p21 (97 vs 78% survival, Po0.0001, hazard ratio ¼ 7.8). Combined high survivin and low p21 values and microsatellite instability high identified a small subgroup with an especially poor prognosis (survival rate 57%, P ¼ 0.01, hazard ratio ¼ 5.6). We conclude that low p21 and high survivin expression are poor prognosis indicators in FIGO stage I endometrial endometrioid adenocarcinoma, especially when high microsatellite instability occurs. Modern Pathology (2011Pathology ( ) 24, 1262Pathology ( -1271 doi:10.1038/modpathol.2011 published online 6 May 2011 Keywords: endometrial cancer; FIGO I; microsatellite instability; prognostic; p21; survivin Endometrial carcinoma is the most frequent gynecological cancer. The disease-related death rate in FIGO stage II-IV is high (20-80% and higher), while in the 'favorable' early stage FIGO I, the death rate ranges from 5 to 15%, 1,2 which has been stable for decades.3 This prompts the search of other prognostic indicators to enable a more accurate triaging

Abstract. Objectives:To analyze the prognostic value of microsatellite instability (MSI) in a population-based study of FIGO stage 1-4 endometrial endometrioid adenocarcinomas.Study design: Survival analysis in 273 patients of MSI status and clinico-pathologic features. Using a highly sensitive pentaplex polymerase chain reaction to establish MSI status, cases were divided into microsatellite stable (MSS), MSI-low (MSI-L, 1 marker positive) and MSI-high (MSI-H, 2-5 markers positive).Results: After 61 months median follow-up (1-209), 34 (12.5%) of the patients developed metastases but only 6.4% of the FIGO 1. MSI (especially as MSI-H vs. MSS/MSI-Lcombined) was prognostic in FIGO 1 but not in FIGO 2-4. The 5 and 10 year recurrence-free survival rates were 98% and 95% in the MSS/MSI-L vs. 85% and 73% in the MSI-H patients (p = 0.005).Conclusions: MSI-H status assessed by pentaplex polymerase chain reaction is an indicator of poor prognosis in FIGO 1, but not in FIGO 2-4 endometrial endometrioid adenocarcinomas.

E Rewcastle et al.PAX2 in endometrial neoplasia 981-991 AbstractIn order to avoid the consequences of over-and under-treatment of endometrial hyperplasia, diagnostic accuracy and progression risk assessment must be improved. The aim of this study was to assess whether PAX2 or PTEN expression could predict progression-free survival in endometrial intraepithelial neoplasia (EIN) and endometrial endometrioid carcinoma (EEC). Immunohistochemistry for detection of PAX2 and PTEN was performed on 348 endometrial samples; 75 proliferative endometrium (PE), 36 EIN and 237 EEC. Cases classified as PTEN null (1 or more glands negatively stained) were more prevalent in EEC than in PE and EIN (64% EEC vs 11% PE/EIN). A progressive decrease in PAX2 expression was observed from PE to EIN to EEC. Long-term clinical follow-up (6-310 months, median: 126) was available for 62 PE cases, all 36 EIN cases and 178 EEC cases. No patients with PE demonstrated progression to EIN or EEC.Progression of disease was observed in 10 (28%) EIN patients. These patients had significantly lower PAX2 expression than those that regressed (P = 0.005). Progression-free survival analysis revealed that EIN patients with a high-risk PAX2 expression score (H-score ≤75) had a higher probability of progression of disease in comparison to those with a low-risk score (H-score >75). PAX2 expression was not prognostic in EEC nor was PTEN status of prognostic value in either EIN or EEC. PAX2 expression analysis by means of H-score has prognostic potential for the identification of high-risk progression cases in EIN but needs to be validated in a larger cohort.Endocrine-Related Cancer (2018) 25, 981-991

Objectives: To analyze the prognostic value of microsatellite instability (MSI) in a population-based study of FIGO stage 1–4 endometrial endometrioid adenocarcinomas.Study Design: Survival analysis in 273 patients of MSI status and clinico-pathologic features. Using a highly sensitive pentaplex polymerase chain reaction to establish MSI status, cases were divided into microsatellite stable (MSS), MSI-low (MSI-L, 1 marker positive) and MSI-high (MSI-H, 2–5 markers positive).Results: After 61 months median follow-up (1-209), 34 (12.5%) of the patients developed metastases but only 6.4% of the FIGO 1. MSI (especially as MSI-H vs. MSS/MSI-Lcombined) was prognostic in FIGO 1 but not in FIGO 2–4. The 5 and 10 year recurrence-free survival rates were 98% and 95% in the MSS/MSI-L vs. 85% and 73% in the MSI-H patients (p=0.005).Conclusions: MSI-H status assessed by pentaplex polymerase chain reaction is an indicator of poor prognosis in FIGO 1, but not in FIGO 2–4 endometrial endometrioid adenocarcinomas.

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