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Objective: To assess the impact of lymphadenectomy and lymphoedema of the lower limbs (LLL) on health‐related quality of life (HRQoL) 1 year after surgery for endometrial cancer (EC). Design: Prospective longitudinal cohort multicentre study. Setting: Departments of obstetrics and gynaecology at four university hospitals, six central hospitals and four county hospitals in Sweden. Population: Two‐hundred‐and‐thirty‐five women with early stage EC were included; 116 with high‐risk EC underwent surgery including lymphadenectomy (+LA), and 119 with low‐risk EC had surgery without lymphadenectomy (−LA). Methods: The generic SF‐36 and EQ‐5D‐3L and the lymphoedema‐specific LYMQOL questionnaire were used to assess HRQoL. LLL was assessed by systematic circumferential measurements of the legs enabling volume estimation, clinical evaluation and patient‐reported perception of leg swelling. All assessments were carried out on four occasions; preoperatively, and 4–6 weeks, 6 months and 1 year postoperatively. Main outcome measure: HRQoL scores. Results: No significant differences were seen in HRQoL between the +LA and –LA groups 1 year postoperatively. Irrespective of method of determining LLL, women with LLL were significantly more affected in the LYMQOL domains Function, Appearance/body image and Physical symptoms, but not in the domain Emotion/mood, than women without LLL. No such differences were seen in the generic HRQoL or in the LYMQOL global score between the groups with and without LLL. Conclusions: Lymphadenectomy did not seem to affect generic HRQoL adversely. Irrespective of the method of measuring, LLL affected the lymphoedema‐specific HRQoL negatively, mainly in physical domains, but had no impact on the generic HRQoL. Lymphoedema has impact on lymphoedema‐specific, but not on generic, HRQoL, 1 year after surgery for EC. Lymphoedema has impact on lymphoedema‐specific, but not on generic, HRQoL, 1 year after surgery for EC. [ABSTRACT FROM AUTHOR]

Background:Preoperative risk stratification is essential in tailoring endometrial cancer treatment, and biomarkers predicting lymph node metastasis and aggressive disease are aspired in clinical practice. DNA ploidy assessment in hysterectomy specimens is a well-established prognostic marker. DNA ploidy assessment in preoperative curettage specimens is less studied, and in particular in relation to the occurrence of lymph node metastasis.Methods:Curettage image cytometry DNA ploidy in relation to established clinicopathological variables and outcome was investigated in 785 endometrial carcinoma patients prospectively included in the MoMaTEC multicentre trial.Results:Diploid curettage status was found in 72.0%, whereas 28.0% were non-diploid. Non-diploid status significantly correlated with traditional aggressive postoperative clinicopathological features, and was an independent predictor of lymph node metastasis among FIGO stage I-III patients in multivariate analysis (OR 1.94, P=0.033). Non-diploid status was related to shorter disease-specific survival (5-year DSS of 74.4% vs 88.8% for diploid curettage, P<0.001). When stratifying by FIGO stage and lymph node status, the prognostic effect remained. However, in multivariate regression analysis, preoperative histological risk classification was a stronger predictor of DSS than DNA ploidy.Conclusions:Non-diploid curettage is significantly associated with aggressive clinicopathological phenotype, lymph node metastasis, and poor survival in endometrial cancer. The prognostic effect was also observed among subgroups with (presumably) less aggressive traits, such as low FIGO stage and negative lymph node status. Our results indicate curettage DNA ploidy as a possible supplement to existing parameters used to tailor surgical treatment. [ABSTRACT FROM AUTHOR]

Abstract Background We aimed to investigate the use of ovarian cyst fluid as a source for biomarker discovery and to find novel biomarkers for use in the diagnosis of epithelial ovarian tumors. Results Ovarian cyst fluids from 218 women were collected and 192 (benign n = 129, malignant n = 63) were analyzed using mass spectrometry. 1180 peaks were detected, 221 of which were differently expressed between benign and malignant ovarian tumors. Seventeen peaks had receiver operating curve and area under the curve values >0.70; the majority of these represented peaks for apolipoproteins C-III and C-I (ApoC-I), transthyretin (TTR), serum amyloid A4 (SAA4), and protein C inhibitor (PCI). ApoC-III, PCI, and serum CA125, with an ROC AUC 0.94 was the best combination for diagnosing epithelial ovarian cancer. ApoC-III and PCI was analyzed with ELISA in the original cohort (n = 40) and in 40 new cyst fluid samples for confirmation with an independent method and validation. Results from MS and ELISA for ApoC-III correlated well (p = 0.04). In the validation set, ApoC-III was significantly (p = 0.001) increased in the malignant epithelial ovarian cancers. Conclusions Fluid from ovarian cysts connected directly to the primary tumor harbor many possible new tumor-specific biomarkers. Biomarkers found in ovarian cyst fluid may be used as molecular imaging targets for early diagnostics and prediction of therapy. Plasma abundant proteins are also influencing the cystic fluid proteome. Methods for isolating less frequent cyst fluid proteins are needed.

Introduction: Minimally invasive methods to reduce menorrhagia were introduced in the 1980s and 1990s. Transcervical endometrial resection (TCRE) and endometrial ablation (EA) are two of the most frequently used methods. As none of them can guarantee a complete removal of the endometrium, there are concerns that the remaining endometrium may develop to endometrial cancer (EC) later in life. The primary aim was to analyze the long-term incidence of EC after TCRE and EA in a nationwide population. The secondary aim was to assess the two treatment modalities separately., Material and Methods: The Swedish National Patient Registry and National Quality Registry for Gynecological Surgery were used for identification of women who had TCRE or EA performed between 1997-2017. The cohort was followed from the first TCRE or EA until hysterectomy, diagnosis of EC, or death. Follow-up data were retrieved from the National Cancer Registry and the National Death Registry. Expected incidence for EC in Swedish women was calculated using Swedish data retrieved from the NORDCAN project after having taken into account differences of age and follow-up time. Cumulative incidence of EC after TCRE and EA, was calculated. A standardized incidence ratio was calculated based on the expected and observed incidence, stratified by age and year of diagnosis., Results: In total, 17 296 women (mean age 45.1 years) underwent TCRE (n = 8626) or EA (n = 8670). Excluded were 3121 who had a hysterectomy for benign causes during follow up. During a median follow-up time of 7.1 years (interquartile range 3.1-13.3 years) the numbers of EC were 25 (0.3%) after TCRE and 2 (0.02%) after EA, respectively. The observed incidence was significantly lower than expected (population-based estimate) after EA but not after TCRE, giving a standardized incidence ratio of 0.13 (95% confidence interval [CI] 0.03-0.53) after EA and 1.27 (95% CI 0.86-1.88) after TCRE. Median times to EC were 3.0 and 8.3 years after TCRE and EA, respectively., Conclusions: There was a significant reduction of EC after EA, suggesting a protective effect, whereas endometrial resection showed an incidence within the expected rate., (© 2022 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background: Poor survival rates in different cancer types are sometimes blamed on diagnostic and treatment delays, and it has been suggested that such delays might be related to sociodemographic factors such as education and ethnicity. We examined associations of the wait time from diagnosis to surgery and survival in endometrial cancer (EC) and explored patient and tumour factors influencing the wait time., Material and Methods: In this historical population-based cohort study, The Swedish Quality Registry for Gynaecologic Cancer (SQRGC) was used to identify EC patients who underwent primary surgery between 2010 and 2018. Factors associated with a wait time > 32 d were analysed with logistic regression. The 32-d time point was defined in accordance with the Swedish Standardisation Cancer Care programme. Adjusted Poisson regression analyses were used to analyse excess mortality rate ratio (EMRR)., Results: Out of 7366 women, 5535 waited > 32 d for surgery and 1098 > 70 d. The overall median wait time was 44 d. The factors most strongly associated with a wait time > 32 d were surgery at a university hospital (adjusted odds ratio [OR] 1.34, 95% confidence interval [CI] 1.08-1.66) followed by country of birth (OR 1.31, 95% CI 1.10-1.55) and year of diagnosis. There were no associations between wait time and histology or age. A wait time < 15 d was associated with higher mortality (adjusted EMRR 2.29,95% CI 1.36-3.84) whereas no negative survival impact was seen with a wait time of 70 d. Age, tumour stage, histology and risk group were highly associated with survival, whereas education, country of origin and hospital level did not have any impact on survival., Conclusions: Surgery within the first two weeks after EC diagnosis was associated with worsened survival. A prolonged wait time did not seem to have any significant adverse effect on prognosis.HighlightsSurgery within the first two weeks after diagnosis of endometrial cancer (EC) was associated with poorer survival.A prolonged wait time to surgery did not worsen prognosis.Delay in time to surgery was associated with sociodemographic factors.

Objective: The aim of the study was to determine risk factors for lymphedema of the lower limbs, assessed by four methods, 1 year after surgery for endometrial cancer., Methods: A prospective longitudinal multicenter study was conducted in 14 Swedish hospitals. 235 women with endometrial cancer were included; 116 underwent surgery including lymphadenectomy, and 119 had surgery without lymphadenectomy. Lymphedema was assessed preoperatively and 1 year postoperatively objectively by systematic circumferential measurements of the legs, enabling volume estimation addressed as (1) crude volume and (2) body mass index-standardized volume, or (3) clinical grading, and (4) subjectively by patient-reported perception of leg swelling. In volume estimation, lymphedema was defined as a volume increase ≥10%. Risk factors were analyzed using forward stepwise logistic regression models and presented as adjusted odds ratio (aOR) and 95% confidence interval (95% CI)., Results: Risk factors varied substantially, depending on the method of determining lymphedema. Lymphadenectomy was a risk factor for lymphedema when assessed by body mass index-standardized volume (aOR 14.42, 95% CI 3.49 to 59.62), clinical grading (aOR 2.11, 95% CI 1.04 to 4.29), and patient-perceived swelling (aOR 2.51, 95% CI 1.33 to 4.73), but not when evaluated by crude volume. Adjuvant radiotherapy was only a risk factor for lymphedema when assessed by body mass index-standardized volume (aOR 15.02, 95% CI 2.34 to 96.57). Aging was a risk factor for lymphedema when assessed by body mass index-standardized volume (aOR 1.07, 95% CI 1.00 to 1.15) and patient-perceived swelling (aOR 1.06, 95% CI 1.02 to 1.10), but not when assessed by crude volume or clinical grading. Increase in body mass index was a risk factor for lymphedema when estimated by crude volume (aOR 1.92, 95% CI 1.36 to 2.71) and patient-perceived swelling (aOR 1.36, 95% CI 1.11 to 1.66), but not by body mass index-standardized volume or clinical grading. The extent of lymphadenectomy was strongly predictive for the development of lymphedema when assessed by body mass index-standardized volume and patient-perceived swelling, but not by crude volume or clinical grading., Conclusion: Apparent risk factors for lymphedema differed considerably depending on the method used to determine lymphedema. This highlights the need for a 'gold standard' method when addressing lymphedema for determining risk factors., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Deep myometrial invasion (≥50%) is a prognostic factor for lymph node metastases and decreased survival in endometrial cancer. There is no consensus regarding which pre/intraoperative diagnostic method should be preferred. Our aim was to explore the pattern of diagnostic methods for myometrial invasion assessment in Sweden and to evaluate differences among magnetic resonance imaging (MRI), transvaginal sonography, frozen section, and gross examination in clinical practice., Material and Methods: This is a nationwide historical cohort study; women with endometrial cancer with data on assessment of myometrial invasion and FIGO stage I-III registered in the Swedish Quality Registry for Gynecologic Cancer (SQRGC) between 2017 and 2019 were eligible. Data on age, histology, FIGO stage, method, and results of myometrial invasion assessment, pathology results, and hospital level were collected from the SQRGC. The final assessment by the pathologist was considered the reference standard., Results: In the study population of 1401 women, 32% (n = 448) had myometrial invasion of 50% of more. The methods reported for myometrial invasion assessment were transvaginal sonography in 59%, MRI in 28%, gross examination in 8% and frozen section in 5% of cases. Only minor differences were found for age and FIGO stage when comparing methods applied for myometrial invasion assessment. The sensitivity, specificity, and accuracy to find myometrial invasion of 50% or more with transvaginal sonography were 65.6%, 80.3%, and 75.8%, for MRI they were 76.9%, 71.9%, and 73.8%, for gross examination they were 71.9%, 93.6%, and 87.3%, and for frozen section they were 90.0%, 92.7%, and 92.0%, respectively., Conclusions: In Sweden, the assessment of deep myometrial invasion is most often performed with transvaginal sonography, but the sensitivity is lower than for the other diagnostic methods. In clinical practice, the accuracy is moderate for transvaginal sonography and MRI., (© 2021 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background: The aim of this study was to analyze overall survival in endometrial cancer patients' FIGO stages I-III in relation to surgical approach; minimally invasive (MIS) or open surgery (laparotomy)., Methods: A population-based retrospective study of 7275 endometrial cancer patients included in the Swedish Quality Registry for Gynecologic Cancer diagnosed from 2010 to 2018. Cox proportional hazard models were used in univariable and multivariable survival analyses., Results: In univariable analysis open surgery was associated with worse overall survival compared with MIS hazard ratio, HR, 1.39 (95% CI 1.18-1.63) while in the multivariable analysis, surgical approach (MIS vs open surgery) was not associated with overall survival after adjustment for known risk factors (HR 1.12, 95% CI 0.95-1.32). Higher FIGO stage, non-endometrioid histology, non-diploid tumors, lymphovascular space invasion and increasing age were independent risk factors for overall survival., Conclusion: The minimal invasive or open surgical approach did not show any impact on survival for patients with endometrial cancer stages I-III when known prognostic risk factors were included in the multivariable analyses.

Aim: The first Swedish National Guidelines for Ovarian Cancer (NGOC) were published in 2012. We aimed to evaluate surgical outcomes and survival in patients with stage IIIC-IV disease, before and after the NGOC implementation., Method: Women with primary epithelial ovarian cancer, FIGO stage IIIC-IV, registered in the Swedish Quality Registry for Gynecologic Cancer 2008-2011 and 2013-2016 were included. Surgical outcomes were analyzed, including frequency of complete cytoreduction (R0). Relative survival (RS) and excess mortality rate ratios (EMRRs) were computed as measures of survival. Univariable and multivariable regression (Poisson) were calculated., Results: In total, 3728 women were identified, 1746 before and 1982 after NGOC. After adjusting for age and stage, survival was improved 2013-2016 vs. 2008-2011 (EMRR 0.89; 95%CI:0.82-0.96, p < 0.05). For women undergoing primary debulking surgery (PDS), R0 frequency (28.9% vs. 53.3%; p < 0.001) and 5-year RS (29.6% (95%CI:26.8-32.8) vs. 37.4% (95%CI:33.6-41.7)) were increased, but fewer patients (58% vs. 44%, p < 0.001) underwent PDS after NGOC implementation. Median survival for the PDS cohort increased from 35 months (95%CI,32.8-39.2) to 43 months (95%CI,40.9-46.4). In the neoadjuvant chemotherapy (NACT) + interval debulking surgery (IDS) cohort, R0 increased (36.8% to 50.1%, p < 0.001), but not 5-year RS (17.5% vs. 20.7%, ns). Compared to PDS, the EMRR was 1.32 (95%CI,1.19-1.47, p < 0.001) for NACT+IDS and 3.00 (95%CI,2.66-3.38, p < 0.001) for chemotherapy alone. In multivariable analyses, PDS, R0, age ≤ 70 years, and stage IIIC were found to be independent factors for improved RS., Conclusion: Implementation of the first National Guidelines for Ovarian Cancer improved relative survival in advanced ovarian cancer., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2021. Published by Elsevier Inc.)

Objective: Vulvar cancer affects mainly elderly women and with an ageing population the incidence has increased. We explored the primary treatment patterns and relative survival of patients with vulvar squamous cell carcinoma (VSCC) by stage and age-group., Methods: A population-based nationwide study on women diagnosed with VSCC between 2012 and 2016 and registered in the Swedish Quality Registry for Gynecologic Cancer (SQRGC). Main outcome was 5-year relative survival (RS) estimated by the Pohar Perme method. The relative risk of excess mortality (EMRR) between different groups was analyzed by Poisson regression. The age-standardized relative survival (AS-RS) was estimated for the total cohort., Results: Median follow-up time was 41 months. The study population included 657 women; 33% were ≥ 80 years old. FIGO stage I was most common (55%). Primary surgery was performed in 96% stage I, 65% stage II, 80% stage III and 28% stage IV. In women ≥80 years, exploration of the groins and chemoradiotherapy was less often performed. They also received lower mean doses of radiation than younger women. The 5-year AS-RS was 74%. 5-year RS was 84% for stage I, 60% for stage II, 54% for stage III and 35% for stage IV. The EMRR for women ≥80 years compared with women <60 years was 4.3 (p < 0.001); 4.9 (p < 0.001) for stages I-II and 3.5(p = 0.007) for stage III., Conclusions: In general, primary treatment of patients with vulvar squamous cell carcinoma in Sweden adhered to guidelines. Areas of improvement include treatment for stage II and for the very old., Competing Interests: Declaration of Competing Interest Dr. Avall-Lundqvist: Honoraria: Roche; Advisory board: Astra Zeneca, Clovis Oncology, Tesaro and Genmab. The other authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: The study aimed to determine the incidence of lower limb lymphedema (LLL) after surgery for endometrial cancer (EC) by means of three methods, and to determine the incidence of lymphocysts after one year., Methods: A prospective longitudinal multicenter study was conducted in 14 hospitals in Sweden. Two-hundred-and-thirty-five women with EC were included; 116 underwent surgery that included lymphadenectomy (+LA) and 119 were without lymphadenectomy (-LA). Lymphedema was assessed objectively on four occasions; preoperatively, at 4-6 weeks, six months and one year postoperatively using systematic measurement of leg circumferences, enabling calculation of leg volumes, and a clinical grading of LLL, and subjectively by the patient's perception of lymphedema measured by a lymphedema-specific quality-of-life instrument. Lymphocyst was evaluated by vaginal ultrasonography., Results: After one year the incidence of LLL after increase in leg volume adjusted for body mass index was 15.8% in +LA women and 3.4% in -LA women. The corresponding figures for clinical grading were 24.1% and 11.8%, and for patient-reported perceived LLL 10.7% and 5.1%. The agreement between the modalities revealed fair to moderate correlation between patient-reported LLL and clinical grading, but poor agreement between volume increase and patient-reported LLL or clinical grading. Lymphocysts were found in 4.3% after one year., Conclusions: Although the incidence of LLL and lymphocysts after surgery for EC including LA seemed to be relatively high the study demonstrated significant variations in incidence depending on the measurement modality. This emphasizes the need for a 'gold standard' of measurement of LLL in clinical practice and research., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The aim of this study is to evaluate the impact of lymphovascular space invasion (LVSI) on the risk of lymph node metastases and survival in endometrioid endometrial adenocarcinoma. Material and methods: As regard the study design, this is a cohort study based on prospectively recorded data. Patients with endometrioid endometrial adenocarcinoma registered in the Swedish Quality Registry for Gynecologic Cancer 2010-2017 with FIGO stages I-III and verified nodal status were identified ( n  = 1587). LVSI together with established risk factors, namely DNA ploidy, FIGO grade, myometrial invasion and age, were included in multivariable regression analyses with lymph node metastases as the dependent variable. Associations between the risk factors and overall and relative survival were included in multivariable models. Estimates of risk ratios (RR), hazard ratios (HR), excess mortality rate ratios (EMR), and 95% confidence intervals (95% CI) were calculated. Results: The presence of LVSI presented the strongest association with lymph node metastases ( RR  = 5.46, CI 3.69-8.07, p  < .001) followed by deep myometrial invasion ( RR  = 1.64, CI 1.13-2.37). In the multivariable survival analyses, LVSI (EMR = 7.69, CI 2.03-29.10,) and non-diploidy (EMR = 3.23, CI 1.25-8.41) were associated with decreased relative survival. In sub-analyses including only patients with complete para-aortic and pelvic lymphadenectomy and negative lymph nodes ( n  = 404), only LVSI ( HR  = 2.50, CI 1.05-5.98) was associated with a worsened overall survival. Conclusion: This large nationwide study identified LVSI as the strongest independent risk factor for lymph node metastases and decreased survival in patients with endometrioid adenocarcinomas. Moreover, decreased overall survival was also seen in patients with LVSI-positive tumors and negative lymph nodes, indicating that hematogenous dissemination might also be important.

Objective: Survival in cervical cancer has improved little over the last decades. We aimed to elucidate primary treatment patterns and survival., Methods: Population-based study of patients included in the Swedish Quality Registry for Gynecologic Cancer diagnosed 2011-2015. Main outcome was 5-year relative survival (RS). Age-standardised RS (AS-RS) was estimated for the total cohort and for the pooled study population of squamous, adenosquamous-, adenocarcinoma., Results: Median follow-up time was 4.6 years. The study population consisted of 2141 patients; 97% of the 2212 patients in the total cohort and the 5-year AS-RS was 71% and 70%, respectively. RS stage IB1: surgery alone 95% vs. 72% for definitive chemoradiotherapy (CT-RT) (p < 0.001). In stage IIA1 74% had CT-RT, and 47% of operated patients received adjuvant (CT)-RT. RS stage IB2: surgically treated 81% (69% received adjuvant (CT)-RT) vs. 76% for (CT)-RT (p = 0.73). RS stage IIB: 77% for CT-RT + brachytherapy (BT), 37% for RT + BT (p = 0.045) and 27% for RT-BT (p < 0.001). Stages III-IVA; <40% received CT-RT + BT, RS 45% vs. 18% for RT-BT (RR 4.1, p < 0.001). RS stage IVB 7%., Conclusion: Primary treatment of cervical cancer in Sweden adhered to evidence-based standard of care. Areas of improvement include optimising treatment for stages III-IVA, and avoiding combining surgery and radiotherapy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: For a few types of cancer, lower socioeconomic status (SES) is associated with higher incidence, and for even more cancer types it is associated with having a less favorable tumor stage at diagnosis. For endometrial cancer (EC), however, there is no clear evidence of such associations with SES. There is a need for analysis of sociodemographic disparities in EC incidences according to stage at diagnosis, which may provide support for trying to improve early detection of EC. Material and methods: Stage-specific incidences of endometrioid and non-endometrioid endometrial carcinomas [EECs (∼90% of all EC cases) and NECs (∼10%)] were analyzed for the population of the Western Swedish Healthcare Region, taking into account year (1995-2016), age, educational level (low, intermediate and high), and immigrant status (Swedish-born, foreign-born). All EC cases were identified and data were obtained from population-based registries. Results: Stage distribution of diagnosed EECs differed significantly according to the educational level of patients who were aged between 50 and 74 years at diagnosis, but not in the case of younger or older patients. An analysis based on 3113 EEC cases aged 50-74 years at diagnosis revealed marked disparities in the stage-II to stage-IV EEC incidences but not in the stage-I EEC incidence. Compared to women with a high level of education, the incidence rate ratios of stage-I, stage-II and stage-III and -IV EEC in women with a low level of education were 1.00 (95% CI: 0.90-1.12), 1.65 (1.13-2.42), and 1.82 (1.33-2.49), respectively. For NEC, we found no such association. Conclusions: Elevated incidences of stage-II to stage-IV EEC in 50- to 74-year-old women with a low level of education suggest that there should be targeted health service trials aimed at improving awareness of EC. Well-targeted EC awareness programs might lead to considerable health benefits.

Objectives: To assess the effects on relative survival of established and new prognostic factors in stage I-III grade 1-3 endometrioid endometrial carcinoma and in the subgroup of stage I grade 1-2., Methods: This was a population-based, retrospective study including all women (n=1113) in the western Swedish healthcare region diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage I-III grade 1-3 endometrioid endometrial carcinoma in 2006-2011. Histology, grade, stage, and age were prospectively reported to the regional clinical and national cancer registers. DNA ploidy and S-phase fraction were analyzed by flow cytometer. S-phase fraction cut-off was set at ≥8%. Tumor biopsies were classified as diploid if there was one G0/G1 peak or the DNA index was 1.0±0.04. Overexpression of p53 as determined by immunohistochemistry was positive if strong nuclear staining was found in >30% of the neoplastic cells., Results: Based on univariable statistical analyses we found that 5-year relative survival was significantly associated with S-phase fraction, DNA ploidy, p53, stage, grade, and age. Excess mortality for S-phase fraction ≥8%, aneuploidy, and p53 overexpression was 8, 14, and 8 and times higher, respectively. However, in a multivariable regression model, adjusted for stage, grade, and age, S-phase fraction, DNA ploidy, and p53 were not statistically independent prognostic factors (p=0.413, p=0.107, p=0.208, respectively) for 5-year relative survival in stage I-III grade 1-3 endometrioid endometrial carcinoma. In a subgroup analysis of stage I grade 1-2, aneuploidy identified a subgroup with impaired 5-year relative survival., Conclusion: We can conclude that S-phase fraction, DNA ploidy, and p53 overexpression did not improve identification of high-risk patients by stage, grade, and age in stage I-III endometrioid endometrial carcinoma. In stage I, aneuploidy and grade 2 predicted lower relative survival rates than other variables., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Several studies have identified L1 cell adhesion molecule (L1CAM) as a strong prognostic marker in endometrial cancer. To further underline the clinical usefulness of this biomarker, we investigated L1CAM as a predictive marker for lymph node metastases and its prognostic impact in curettage specimens and preoperative plasma samples. In addition, we aimed to validate the prognostic value of L1CAM in hysterectomy specimen., Methods: Immunohistochemical staining of L1CAM was performed for 795 hysterectomy and 1134 curettage specimen from endometrial cancer patients. The L1CAM level in preoperative blood samples from 372 patients was determined using ELISA., Results: Expression of L1CAM in curettage specimen was significantly correlated to L1CAM level in corresponding hysterectomy specimen (P<0.001). Both in curettage and preoperative plasma samples L1CAM upregulation was significantly associated with features of aggressive disease and poor outcome (P<0.001). The L1CAM was an independent predictor of lymph node metastases, after correction for curettage histology, both in curettage specimen (P=0.002) and plasma samples (P=0.048). In the hysterectomy samples L1CAM was significantly associated with poor outcome (P<0.001)., Conclusions: We demonstrate that preoperative evaluation of L1CAM levels, both in curettage or plasma samples, predicts lymph node metastases and adds valuable information on patient prognosis.

Surgery is the cornerstone in primary endometrial cancer treatment, and with curative intent it constitutes total hysterectomy and bilateral salpingo-oopherectomy. In addition, lymphadenectomy is performed in selected patients dependent on a preoperative risk assessment. Recent reports from the surgical approach to esophageal cancer reveal worse outcome when esophagectomy is performed later in the week. On this basis, we set out to explore weekday of surgery in relation to long-term outcome in 1302 endometrial cancer patients prospectively included in the MoMaTEC multicenter study. Day of surgery was dichotomized as early-week (Monday-Tuesday) or late-week (Wednesday-Friday), and evaluated as a discrete variable. Adjusted for patient age, Body Mass Index (BMI), FIGO stage, and histology, surgery performed later in the week was associated with 50.9% increased risk of all-cause death (p = 0.029). Among high-stage patients (FIGO stage III and IV), 5-year disease-specific survival proportions were 53.0% for early-week operated vs. 40.2% for late-week operated (p = 0.005 for difference). In multivariate survival analysis of high-stage patients, late-week surgery correlated with an increased risk of disease-specific death by 88.7% and all-cause death by 76.4% (p<0.017). Evaluating only patients who underwent lymphadenectomy, the adverse prognostic effect of being operated late-week remained for both disease-specific and all-cause death (HR 2.151 and HR 1.912, p = 0.004). Whether surgery was performed early- or late-week was not influenced by patient age, BMI, preoperative histology risk classification, FIGO stage or postoperative histology (all p>0.05). In conclusion, endometrial cancer surgery conducted late-week is associated with worse long-term outcome. Our findings are most evident among patients with higher FIGO stages, and patients who underwent more extensive surgical procedure (lymphadenectomy). With support from other studies, our results suggest that high-risk patients may benefit from surgery earlier in the week.

Objective: To evaluate if increased individualization in endometrial cancer classification/treatment affected relative survival., Methods: The present retrospective register-based population study included data from all women in the western Swedish healthcare region who were treated for endometrial cancer between January 1, 1995, and December 31, 2011. Outcomes and prognostic data were retrieved from the western Swedish healthcare region's cancer and clinical endometrial cancer registries. Patients were stratified based on two different treatment programs (cohort 1 January 1, 1995, to September 10, 2006, and cohort 2 September 11, 2006, to December 31, 2011) and relative survival was compared., Results: Data from 4338 patients were included; 2936 in cohort 1 and 1402 in cohort 2. Among endometrioid endometrial carcinomas, the 5-year relative survival rate for did not differ significantly between the groups (P=0.751); radiotherapy was used more frequently in cohort 1 (P<0.001). Among non-endometrioid endometrial carcinomas, relative survival was lower in cohort 1 (P=0.006); radiotherapy use was more frequent in cohort 1 and chemotherapy use was more frequent in cohort 2 (P=0.001)., Conclusion: Increased individualization in endometrioid endometrial cancer management did not improve relative survival. Improved relative survival was observed for non-endometrioid endometrial cancer; possibly due to increased adjuvant chemotherapy use. This article is protected by copyright. All rights reserved., (This article is protected by copyright. All rights reserved.)

Background: Most endometrial carcinoma patients are diagnosed at an early stage with a good prognosis. However, a relatively low fraction with lethal disease constitutes a substantial number of patients due to the high incidence rate. Preoperative identification of patients with high risk and low risk for poor outcome is necessary to tailor treatment. Nucleotyping refers to characterization of cell nuclei by image cytometry, including the assessment of chromatin structure by nuclear texture analysis. This method is a strong prognostic marker in many cancers but has not been evaluated in preoperative curettage specimens from endometrial carcinoma., Methods: The prognostic impact of changes in chromatin structure quantified with Nucleotyping was evaluated in preoperative curettage specimens from 791 endometrial carcinoma patients prospectively included in the MoMaTEC multicenter trial., Results: Nucleotyping was an independent prognostic marker of disease-specific survival in preoperative curettage specimens among patients with Federation Internationale des Gynaecologistes et Obstetristes (FIGO) stage I-II disease (HR=2.9; 95% CI, 1.2-6.5; P = 0.013) and significantly associated with age, FIGO stage, histologic type, histologic grade, myometrial infiltration, lymph node status, curettage histology type, and DNA ploidy., Conclusions: Nucleotyping in preoperative curettage specimens is an independent prognostic marker for disease-specific survival, with potential to supplement existing parameters for risk stratification to tailor treatment., Impact: This is the first study to evaluate the prognostic impact of Nucleotyping in curettage specimens from endometrial carcinoma and shows that this may be a clinically useful prognostic marker in endometrial cancer. External validation is warranted. Cancer Epidemiol Biomarkers Prev; 26(1); 61-67. ©2016 AACR., (©2016 American Association for Cancer Research.)

Myosin-1C (MYO1C) is a tumor suppressor candidate located in a region of recurrent losses distal to TP53. Myo1c can tightly and specifically bind to PIP2, the substrate of Phosphoinositide 3-kinase (PI3K), and to Rictor, suggesting a role for MYO1C in the PI3K pathway. This study was designed to examine MYO1C expression status in a panel of well-stratified endometrial carcinomas as well as to assess the biological significance of MYO1C as a tumor suppressor in vitro. We found a significant correlation between the tumor stage and lowered expression of MYO1C in endometrial carcinoma samples. In cell transfection experiments, we found a negative correlation between MYO1C expression and cell proliferation, and MYO1C silencing resulted in diminished cell migration and adhesion. Cells expressing excess of MYO1C had low basal level of phosphorylated protein kinase B (PKB, a.k.a. AKT) and cells with knocked down MYO1C expression showed a quicker phosphorylated AKT (pAKT) response in reaction to serum stimulation. Taken together the present study gives further evidence for tumor suppressor activity of MYO1C and suggests MYO1C mediates its tumor suppressor function through inhibition of PI3K pathway and its involvement in loss of contact inhibition., Competing Interests: The authors have declared that no competing interests exist.

Endometrial cancer is the most common gynecological cancer in developed countries and the observed rise in incidence is mainly caused by life style factors including obesity and diabetes. The management of the disease has undergone major changes in the past 5-10 years. Morphological and genetic studies constitute the basis for the new classification of the disease, and data emerging from the Cancer Genome Atlas suggest that genomic patterns differ within the two types of endometrial cancer. The prognosis seems to be related to occult lymphatic spread but the role of lymphadenectomy is heavily debated. Development of novel biomarkers, sentinel lymph node technique and refined radiological methods may reduce the need of comprehensive staging in the future. The results from the Cancer Genome Atlas suggest that women with endometrial cancer may benefit from »targeted therapies« in the evolving era of personalised medicine.

Background: Preoperative histologic examination of tumour tissue is essential when deciding if endometrial cancer surgery should include lymph node sampling. We wanted to investigate if biomarkers could improve prediction of lymph node metastasis and outcome., Patients and Methods: Curettage specimens from 832 endometrial carcinoma patients prospectively recruited from 10 centres in the MoMaTEC trial (Molecular Markers in Treatment of Endometrial Cancer) were investigated for hormone receptor and p53 status., Results: Eighteen per cent of tumours were double negative for oestrogen- and progesterone receptors (ER/PR loss), 24% overexpressed p53. Pathologic expression of all markers correlated with nodal metastases, high FIGO (Federation International of Gynecology and Obstetrics) stage, non-endometrioid histology, high grade and poor prognosis (all P<0.001). ER/PR loss independently predicted lymph node metastasis (odds ratios (OR) 2.0, 95% confidence interval (CI) 1.1-3.7) adjusted for preoperative curettage histology and predicted poor disease-specific survival adjusted for age, FIGO stage, histologic type, grade and myometrial infiltration (hazard ratio (HR) 2.3, 95% CI 1.4-3.9). For lymph node negative endometrioid tumours, ER/PR loss influenced survival independent of grade., Conclusion: Double negative hormone receptor status in endometrial cancer curettage independently predicts lymph node metastasis and poor prognosis in a prospective multicentre setting. Implementing hormone receptor status to improve risk-stratification for selecting patients unlikely to benefit from lymphadenectomy seems justified., (Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Endometrial cancer patients may benefit from systemic adjuvant chemotherapy, alone or in combination with targeted therapies. Prognostic and predictive markers are needed, however, to identify patients amenable for these therapies., Methods: Primary endometrial tumors were genotyped for >100 hot spot mutations in genes potentially acting as prognostic or predictive markers. Mutations were correlated with tumor characteristics in a discovery cohort, replicated in independent cohorts and finally, confirmed in the overall population (n=1063)., Results: PIK3CA, PTEN and KRAS mutations were most frequently detected, respectively in 172 (16.2%), 164 (15.4%) and 161 (15.1%) tumors. Binary logistic regression revealed that PIK3CA mutations were more common in high-grade tumors (OR=2.03; P=0.001 for grade 2 and OR=1.89; P=0.012 for grade 3 compared to grade 1), whereas a positive TP53 status correlated with type II tumors (OR=11.92; P<0.001) and PTEN mutations with type I tumors (OR=19.58; P=0.003). Conversely, FBXW7 mutations correlated with positive lymph nodes (OR=3.38; P=0.045). When assessing the effects of individual hot spot mutations, the H1047R mutation in PIK3CA correlated with high tumor grade and reduced relapse-free survival (HR=2.18; P=0.028)., Conclusions: Mutations in PIK3CA, TP53, PTEN and FBXW7 correlate with high tumor grade, endometrial cancer type and lymph node status, whereas PIK3CA H1047R mutations serve as prognostic markers for relapse-free survival in endometrial cancer patients., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: The MDM2 promoter polymorphism (SNP309T > G) extends a binding site for the transcription factor Sp1 and has been linked to elevated cancer risk and/or young age at cancer diagnosis, especially in females. Recently, we reported an adjacent polymorphism (SNP285G > C). SNP285C antagonises the effect of SNP309G by reducing Sp1 binding and lowers the risk of breast and ovarian cancer., Methods: We assessed the potential gender specificity in the effect of this polymorphism. We performed in silico predictions of transcription factor binding sites in the MDM2 promoter and analysed MDM2 SNP285 and SNP309 status in two independent cohorts of endometrial (n = 438 and 472) and 666 prostatic cancer patients, and compared to 3.140 healthy controls., Results: We identified three oestrogen-receptor binding elements (EREs) within the MDM2 intronic promoter, one of which overlapping the Sp1 binding-site harbouring SNP285. The SNP285C/309G haplotype was associated with a reduced Odds Ratio (OR) for endometrial cancer (OR1: 0.55; Confidence Interval (CI) 0.32-0.97; OR2: 0.65; CI 0.40-1.08, especially for ER+ tumours; OR: 0.48; CI 0.28-0.87) but not for prostatic cancer among SNP309TG heterozygotes. SNP309G (SNP309TG or SNP309GG genotype) was associated with a moderately increased risk of endometrial cancer (OR: 1.17; CI 1.00-1.37) compared to SNP309TT homozygotes. Removing individuals harbouring the SNP309G-counteracting SNP285C polymorphism from the analysis strengthened this association (OR: 1.20; CI 1.02-1.41)., Conclusion: The finding of an ERE overlapping with the Sp1-binding site affected by SNP285, taken together with the significant impact of SNP285 on the risk of breast, ovarian and now endometrial cancer but not prostatic cancer, suggests a gender specific effect of SNP285C on cancer risk., (Copyright © 2011 Elsevier Ltd. All rights reserved.)