Expression patterns of mismatch repair proteins in cervical cancer uncover independent prognostic value of MSH-2.

OBJECTIVE: Although early-detected cervical cancer is associated with good survival, the prognosis for late-stage disease is poor and treatment options are sparse. Mismatch repair deficiency (MMR-D) has surfaced as a predictor of prognosis and response to immune checkpoint inhibitor(s) in several cancer types, but its value in cervical cancer remains unclear. This study aimed to define the prevalence of MMR-D in cervical cancer and assess the prognostic value of MMR protein expression. METHODS: Expression of the MMR proteins MLH-1, PMS-2, MSH-2, and MSH-6 was investigated by immunohistochemical staining in a prospectively collected cervical cancer cohort (n=508) with corresponding clinicopathological and follow-up data. Sections were scored as either loss or intact expression to define MMR-D, and by a staining index, based on staining intensity and area, evaluating the prognostic potential. RNA and whole exome sequencing data were available for 72 and 75 of the patients and were used for gene set enrichment and mutational analyses, respectively. RESULTS: Five (1%) tumors were MMR-deficient, three of which were of neuroendocrine histology. MMR status did not predict survival (HR 1.93, p=0.17). MSH-2 low (n=48) was associated with poor survival (HR 1.94, p=0.02), also when adjusting for tumor stage, tumor type, and patient age (HR 2.06, p=0.013). MSH-2 low tumors had higher tumor mutational burden (p=0.003) and higher frequency of (frameshift) mutations in the double-strand break repair gene RAD50 (p<0.01). CONCLUSION: MMR-D is rare in cervical cancer, yet low MSH-2 expression is an independent predictor of poor survival.

Epstein-Barr Virus and Clinico-Endoscopic Characteristics of Gastric Remnant Cancers Compared to Proximal Non-Remnant Cancers: A Population-Based Study.

Epstein-Barr virus (EBV) is associated with 5-10% of gastric cancers and is recognized as a distinct molecular subtype. EBV positivity is particularly high in gastric remnant cancer (GRC), which may inform the mode of clinical presentation and findings at endoscopy. Most data are from the East, and the question remains how this applies to a Western cohort. We conducted a population-based study in Central Norway, 2001-2016. Patients with GRC (n = 78) and patients with non-GRC proximally located cancer and available tissue for EBV status (n = 116, control group) were identified from the Norwegian Cancer Registry. Relevant data were collected from the individual patient journals. EBV status was assessed using in situ hybridization. The median latency time from the distal gastrectomy to GRC was 37.6 (range 15.7-68.0) years. GRC more often presented with GI bleeding, 31.0% vs. 16.1%, p = 0.017, and at endoscopy more seldom with an ulcer, 19.7% vs. 38.2%, p = 0.012, or a tumour, 40.8% vs. 66.4%, p < 0.001. For GRC, 18.7% were EBV-positive compared to 6.0% among the controls, p = 0.006. EBV status was not associated with patient age, sex, or Lauren histological type. No difference in long-term survival rates between GRC and controls was found or between EBV-positive vs. -negative GRCs. In conclusion, a higher proportion of GRC cases, compared to controls, are EBV positive, indicating different causative factors. The mode of clinical presentation and findings at endoscopy were more subtle in the patients with GRC.

Radiomic profiles improve prognostication and reveal targets for therapy in cervical cancer.

Cervical cancer (CC) is a major global health problem with 570,000 new cases and 266,000 deaths annually. Prognosis is poor for advanced stage disease, and few effective treatments exist. Preoperative diagnostic imaging is common in high-income countries and MRI measured tumor size routinely guides treatment allocation of cervical cancer patients. Recently, the role of MRI radiomics has been recognized. However, its potential to independently predict survival and treatment response requires further clarification. This retrospective cohort study demonstrates how non-invasive, preoperative, MRI radiomic profiling may improve prognostication and tailoring of treatments and follow-ups for cervical cancer patients. By unsupervised clustering based on 293 radiomic features from 132 patients, we identify three distinct clusters comprising patients with significantly different risk profiles, also when adjusting for FIGO stage and age. By linking their radiomic profiles to genomic alterations, we identify putative treatment targets for the different patient clusters (e.g., immunotherapy, CDK4/6 and YAP-TEAD inhibitors and p53 pathway targeting treatments).

Early Gastric Cancers in Central Norway 2001 to 2016-A Population-Based Study.

Early gastric cancers (EGCs) are confined to the gastric mucosa and submucosa irrespective of lymph node metastases and constitute only a minor proportion of gastric cancer in Western countries. We aimed to characterize EGCs and assess the survival of EGC in Central Norway during 2001-2016. A retrospective population-based study on 1205 patients with gastric cancer was performed. At the time, surgical resection was the standard treatment, and 88 (7.3%) EGCs were identified. Histopathological specimens were re-examined, and the eCura score and survival were evaluated. The number of gastric cancers declined (p = 0.010), but the relative proportion of EGC was unchanged during the study period. EGCs were more often of the Lauren intestinal type (p < 0.001) compared with controls. A significant proportion (9.4%, n = 5) of the patients with a low-risk eCura had lymph node metastases, whereas further exclusion of tumors with histological ulceration or SM2 invasion identified an N0 cohort. The median survival for EGC patients was 117.1 months (95% CI 99.8-134.3) and the 5-year overall survival was 75%. Twelve deaths were cancer-related, either due to postoperative complications (5.7%, n = 5) or cancer recurrence (8%, n = 7). In conclusion, EGCs constituted a minor but constant proportion of gastric cancers. eCura alone was insufficient in predicting patients with pN0 disease.

Age-related phenotypes in breast cancer: A population-based study.

Breast cancer in young (<40 years) is associated with a higher frequency of aggressive tumor types and poor prognosis. It remains unclear if there is an underlying age-related biology that contributes to the unfavorable outcome. We aim to investigate the relationship between age and breast cancer biology, with emphasis on proliferation. Clinico-pathologic information, immunohistochemical markers and follow-up data were obtained for all patients aged <50 (Bergen cohort-1; n = 355, not part of a breast screening program) and compared to previously obtained information on patients aged 50 to 69 years (Bergen cohort-2; n = 540), who participated in the Norwegian Breast Cancer Screening Program. Young breast cancer patients presented more aggressive tumor features such as hormone receptor negativity, HER2 positivity, lymph-node metastasis, the HER2-enriched and triple-negative subtypes and shorter survival. Age <40 was significantly associated with higher proliferation (by Ki67). Ki67 showed weaker prognostic value in young patients. We point to aggressive phenotypes and increased tumor cell proliferation in breast cancer of the young. Hence, tumors of young breast cancer patients may present unique biological features, also when accounting for screen/interval differences, that may open for new clinical opportunities, stratifying treatment by age.

Gastric remnant cancer and long-term survival in Central Norway 2001 to 2016 - A population-based study.

INTRODUCTION: Gastric remnant cancer (GRC) has been defined as a distinct clinical entity and is reported to account for 1-8% of all gastric cancers. We aimed to characterize GRC patients and assess survival in a Western population. METHODS: Retrospective population-based cohort study including 1217 patients diagnosed with gastric adenocarcinoma in Central Norway 2001-2016. GRCs (n = 78) defined as adenocarcinomas arising in the residual stomach after distal gastrectomy were compared to non-GRC (n = 1139) and to proximal non-GRC (n = 595). RESULTS: 78 (6.4 %) gastric cancers were GRC. The annual number and proportion of GRC declined during the study period (p = 0.003). Median latency from distal gastrectomy to GRC diagnosis was 37.6 years (15.7-68.0) and previous Billroth II reconstruction was most common (87.7%). Compared to controls, GRC patients were more frequently males (83.3%), diagnosed in earlier TNM stages and were older at diagnosis. A smaller proportion of GRC patients received perioperative or palliative chemotherapy, but the R0/R1resection rate of 41.0% was no different from non-GRC patients. Overall median survival for GRC patients irrespective of treatment was 7.0 months, which did not differ from non-GRCs or proximal non-GRC. In multivariate analyses TNM stage and age were independently associated with mortality, whereas GRC per se was not. CONCLUSIONS: Numbers of GRCs declined during the study period, but the latency between distal gastrectomy and GRC diagnosis was long. GRC patients were more frequently male and older than other gastric cancer patients. GRC was not independently associated with survival after adjusting for TNM stage and tumor location.

Cumulative incidence of first recurrence after curative treatment of stage I-III colorectal cancer. Competing risk analyses of temporal and anatomic patterns.

BACKGROUND: Updated knowledge about the rates of recurrence and time to recurrence following curative treatment of colorectal cancer is essential to secure better patient information on prognosis, to serve as a premise in the discussion on adjuvant chemotherapy, and help to properly scale the intensity and length of follow-up. METHODS: This is a population-based study investigating aspects on first recurrence after radical treatment of clinical stages I-III of colorectal cancer in Central-Norway during 2001-2015. To reveal any time-trends, data were stratified by the time periods 2001-2005, 2006-2010 and 2011-2015. The cumulative incidence of first recurrence was calculated, treating death of unrelated causes as a competing event. Multivariable Cox analyses were done to calculate cause specific hazard ratios (HR) for risk of recurrence. RESULTS: At a minimum follow-up of six years, a first recurrence was detected in 1,113/5,556 patients at risk (20.0%). The recurrence rate was reduced from 23.6% in the first time period, through 20.0% in the second, and to 17.2% in the last, p < 0.001. The reduction applied to all tumor locations, to pathological disease stages II and III, to both gender, across different tumor differentiations, and to both elective and emergency surgery. In multivariable analyses time period, gender, disease stage, and tumor differentiation were significant determinants for risk of recurrence. CONCLUSIONS: The rate of first recurrence after curative surgery for colorectal cancer was substantially reduced from 2001 to 2015. The reason for the reduction could not be attributed to a single factor only. A combined effect of several incremental improvements, such as an increased use of preoperative radiation for rectal cancers, improved adjuvant chemotherapy for colon cancer, and a reduced proportion of emergency surgery, is suggested.

Practice patterns in diagnostics, staging, and management strategies of gallbladder cancer among Nordic tertiary centers.

BACKGROUND AND OBJECTIVE: Gallbladder cancer (GBC) is a rare malignancy in the Nordic countries and no common Nordic treatment guidelines exist. This study aimed to characterize the current diagnostic and treatment strategies in the Nordic countries and disclose differences in these strategies. METHODS: This was a survey study with a cross-sectional questionnaire of all 19 university hospitals providing curative-intent surgery for GBC in Sweden, Norway, Denmark, and Finland. RESULTS: In all Nordic countries except Sweden, neoadjuvant/downstaging chemotherapy was used in GBC patients. In T1b and T2, majority of the centers (15-18/19) performed extended cholecystectomy. In T3, majority of the centers (13/19) performed cholecystectomy with resection of segments 4b and 5. In T4, majority of the centers (12-14/19) chose palliative/oncological care. The centers in Sweden extended lymphadenectomy beyond the hepatoduodenal ligament, whereas all other Nordic centers usually limited lymphadenectomy to the hepatoduodenal ligament. All Nordic centers except those in Norway used adjuvant chemotherapy routinely for GBC. There were no major differences between the Nordic centers in diagnostics and follow-up. CONCLUSIONS: The surgical and oncological treatment strategies of GBC vary considerably between the Nordic centers and countries.

PIK3CA mutations and their impact on survival outcomes of patients with endometrial cancer: A systematic review and meta-analysis.

Several studies have highlighted the frequent alterations of the PI3K pathway in endometrial cancer leading to increased signaling activation with potential for targeted treatment. The objective of this meta-study was to evaluate how PIK3CA exon 9/20 mutations affect survival in endometrial cancer patients, based on available literature. Topic-based search strategies were applied to databases including CENTRAL, MEDLINE, Embase, Web of Science and COSMIC. All studies assessing the impact of mutations in exon 9 and exon 20 of PIK3CA on survival rates of endometrial cancer patients were selected for inclusion. Statistical meta-analysis was performed with the 'meta' package in RStudio. Overall, 7 of 612 screened articles were included in the present study, comprising 1098 women with endometrial cancer. Meta-analysis revealed a tendency of impaired survival for patients with PIK3CA exon 9 and/or exon 20 mutations (RR 1.28; 95% CI 0.84, 1.94; p = 0.25). This tendency was consistent in subgroup analyses stratified by histologic type or -grade, with the most prominent effect in low-grade endometrial cancers (RR 2.04; 95% CI 0.90, 4.62; p = 0.09). In summary, these results suggest that PIK3CA mutations negatively influence survival outcomes of patients with endometrial cancer, including those with low-grade tumors.

Mismatch repair markers in preoperative and operative endometrial cancer samples; expression concordance and prognostic value.

BACKGROUND: The endometrial cancer mismatch repair (MMR) deficient subgroup is defined by loss of MSH6, MSH2, PMS2 or MLH1. We compare MMR status in paired preoperative and operative samples and investigate the prognostic impact of differential MMR protein expression levels. METHODS: Tumour lesions from 1058 endometrial cancer patients were immunohistochemically stained for MSH6, MSH2, PMS2 and MLH1. MMR protein expression was evaluated as loss or intact to determine MMR status, or by staining index to evaluate the prognostic potential of differential expression. Gene expression data from a local (n = 235) and the TCGA (n = 524) endometrial cancer cohorts was used for validation. RESULTS: We identified a substantial agreement in MMR status between paired curettage and hysterectomy samples. Individual high expression of all four MMR markers associated with non-endometrioid subtype, and high MSH6 or MSH2 strongly associated with several aggressive disease characteristics including high tumour grade and FIGO stage, and for MSH6, with lymph node metastasis. In multivariate Cox analysis, MSH6 remained an independent prognostic marker, also within the endometrioid low-grade subgroup (P < 0.001). CONCLUSION: We demonstrate that in addition to determine MMR status, MMR protein expression levels, particularly MSH6, may add prognostic information in endometrial cancer.

Surgery for degenerative cervical myelopathy in patients with rheumatoid arthritis and ankylosing spondylitis: a nationwide registry-based study with patient-reported outcomes.

PURPOSE: To compare patient-reported outcomes (PROMs) following surgery for degenerative cervical myelopathy (DCM) among patients with rheumatoid arthritis (RA) or ankylosing spondylitis (AS) versus those without rheumatic diseases. METHODS: Data were obtained from the Norwegian Registry for Spine Surgery. The primary outcome was change in the Neck Disability Index (NDI) at 1 year. Secondary endpoints included the European Myelopathy Score (EMS), quality of life (EuroQoL-5D [EQ-5D]), numeric rating scales (NRS) for headache, neck pain, and arm pain, and complications. RESULTS: Among 905 participants operated between 2012 and 2018, 35 had RA or AS. There were significant improvements in all PROMs at 1 year and no statistically significant difference between the cohorts in mean change in NDI (- 0.64, 95% CI - 8.1 to 6.8, P = .372), EQ-5D (0.10, 95% CI - 0.04 to 0.24, P = .168), NRS neck pain (- 0.8, 95% CI - 2.0 to 0.4, P = .210), NRS arm pain (- 0.6, 95% CI - 1.9 to 0.7, P = .351), and NRS headache (- 0.5, 95% CI - 1.7 to 0.8, P = .460). DISCUSSION AND CONCLUSION: Our study adds to the limited available evidence that surgical treatment cannot only arrest further progression of myelopathy but also improve functional status, neurological outcomes, and quality of life in patients with rheumatic disease.

Effect of Spinal Cord Burst Stimulation vs Placebo Stimulation on Disability in Patients With Chronic Radicular Pain After Lumbar Spine Surgery: A Randomized Clinical Trial.

Importance: The use of spinal cord stimulation for chronic pain after lumbar spine surgery is increasing, yet rigorous evidence of its efficacy is lacking. Objective: To investigate the efficacy of spinal cord burst stimulation, which involves the placement of an implantable pulse generator connected to electrodes with leads that travel into the epidural space posterior to the spinal cord dorsal columns, in patients with chronic radiculopathy after surgery for degenerative lumbar spine disorders. Design, Setting, and Participants: This placebo-controlled, crossover, randomized clinical trial in 50 patients was conducted at St Olavs University Hospital in Norway, with study enrollment from September 5, 2018, through April 28, 2021. The date of final follow-up was May 20, 2022. Interventions: Patients underwent two 3-month periods with spinal cord burst stimulation and two 3-month periods with placebo stimulation in a randomized order. Burst stimulation consisted of closely spaced, high-frequency electrical stimuli delivered to the spinal cord. The stimulus consisted of a 40-Hz burst mode of constant-current stimuli with 4 spikes per burst and an amplitude corresponding to 50% to 70% of the paresthesia perception threshold. Main Outcomes and Measures: The primary outcome was difference in change from baseline in the self-reported Oswestry Disability Index (ODI; range, 0 points [no disability] to 100 points [maximum disability]; the minimal clinically important difference was 10 points) score between periods with burst stimulation and placebo stimulation. The secondary outcomes were leg and back pain, quality of life, physical activity levels, and adverse events. Results: Among 50 patients who were randomized (mean age, 52.2 [SD, 9.9] years; 27 [54%] were women), 47 (94%) had at least 1 follow-up ODI score and 42 (84%) completed all stimulation randomization periods and ODI measurements. The mean ODI score at baseline was 44.7 points and the mean changes in ODI score were -10.6 points for the burst stimulation periods and -9.3 points for the placebo stimulation periods, resulting in a mean between-group difference of -1.3 points (95% CI, -3.9 to 1.3 points; P = .32). None of the prespecified secondary outcomes showed a significant difference. Nine patients (18%) experienced adverse events, including 4 (8%) who required surgical revision of the implanted system. Conclusions and Relevance: Among patients with chronic radicular pain after lumbar spine surgery, spinal cord burst stimulation, compared with placebo stimulation, after placement of a spinal cord stimulator resulted in no significant difference in the change from baseline in self-reported back pain-related disability. Trial Registration: ClinicalTrials.gov Identifier: NCT03546738.

A radiogenomics application for prognostic profiling of endometrial cancer.

Prognostication is critical for accurate diagnosis and tailored treatment in endometrial cancer (EC). We employed radiogenomics to integrate preoperative magnetic resonance imaging (MRI, n = 487 patients) with histologic-, transcriptomic- and molecular biomarkers (n = 550 patients) aiming to identify aggressive tumor features in a study including 866 EC patients. Whole-volume tumor radiomic profiling from manually (radiologists) segmented tumors (n = 138 patients) yielded clusters identifying patients with high-risk histological features and poor survival. Radiomic profiling by a fully automated machine learning (ML)-based tumor segmentation algorithm (n = 336 patients) reproduced the same radiomic prognostic groups. From these radiomic risk-groups, an 11-gene high-risk signature was defined, and its prognostic role was reproduced in orthologous validation cohorts (n = 554 patients) and aligned with The Cancer Genome Atlas (TCGA) molecular class with poor survival (copy-number-high/p53-altered). We conclude that MRI-based integrated radiogenomics profiling provides refined tumor characterization that may aid in prognostication and guide future treatment strategies in EC.

Gastric Cancers Missed at Upper Endoscopy in Central Norway 2007 to 2016-A Population-Based Study.

BACKGROUND: The rates of missed gastric cancers (MGC) at upper endoscopy (UE) has been reported at 5-10% in Western countries. We aimed to calculate the rate of MGC and identify factors associated with MGC. METHODS: Retrospective population-based cohort study including 730 patients diagnosed with gastric adenocarcinoma in Central Norway 2007-2016. MGCs were incident gastric adenocarcinomas diagnosed 6-36 months after a previous UE. Factors associated with MGC were examined. Definitely missed (UE 6-12 months prior) and potentially missed (UE 12-36 months prior) MGCs were compared. RESULTS: Sixty-seven (9.2%) of 730 gastric cancers were MGC. MGC were associated with localization (p = 0.009) and more frequent in the corpus, Lauren's histological type (p = 0.028) and diffuse type more prevalent, and previous Billroth 2-operation (14.9% vs. 4.7%, p = 0.001). MGCs were diagnosed at earlier stages (p = 0.037). An ulceration was more common in patients with definitely missed than potentially MGC (40.9% vs. 17.8%, p = 0.041). CONCLUSIONS: MGC accounted for 9.2% of gastric cancers in Central Norway. MGC were associated with localization in the corpus, Lauren´s diffuse type and previous Billroth-2-operation. Intensified follow-up and adequate biopsy sampling of patients with gastric ulcerations could reduce the rate of missed gastric cancers.

A Gene Signature Identifying CIN3 Regression and Cervical Cancer Survival.

The purpose of this study was to establish a gene signature that may predict CIN3 regression and that may aid in selecting patients who may safely refrain from conization. Oncomine mRNA data including 398 immune-related genes from 21 lesions with confirmed regression and 28 with persistent CIN3 were compared. L1000 mRNA data from a cervical cancer cohort was available for validation (n = 239). Transcriptomic analyses identified TDO2 (p = 0.004), CCL5 (p < 0.001), CCL3 (p = 0.04), CD38 (p = 0.02), and PRF1 (p = 0.005) as upregulated, and LCK downregulated (p = 0.01) in CIN3 regression as compared to persistent CIN3 lesions. From these, a gene signature predicting CIN3 regression with a sensitivity of 91% (AUC = 0.85) was established. Transcriptomic analyses revealed proliferation as significantly linked to persistent CIN3. Within the cancer cohort, high regression signature score associated with immune activation by Gene Set enrichment Analyses (GSEA) and immune cell infiltration by histopathological evaluation (p < 0.001). Low signature score was associated with poor survival (p = 0.007) and large tumors (p = 0.01). In conclusion, the proposed six-gene signature predicts CIN regression and favorable cervical cancer prognosis and points to common drivers in precursors and cervical cancer lesions.

Simultaneous Resection of Primary Colorectal Cancer and Synchronous Liver Metastases: Contemporary Practice, Evidence and Knowledge Gaps.

The timing of surgical resection of synchronous liver metastases from colorectal cancer has been debated for decades. Several strategies have been proposed, but high-level evidence remains scarce. Simultaneous resection of the primary tumour and liver metastases has been described in numerous retrospective audits and meta-analyses. The potential benefits of simultaneous resections are the eradication of the tumour burden in one procedure, overall shorter procedure time, reduced hospital stay with the likely benefits on quality of life and an expected reduction in the use of health care services compared to staged procedures. However, concerns about accumulating complications and oncological outcomes remain and the optimal selection criteria for whom simultaneous resections are beneficial remains undetermined. Based on the current level of evidence, simultaneous resection should be restricted to patients with a limited liver tumour burden. More high-level evidence studies are needed to evaluate the quality of life, complication burden, oncological outcomes, as well as overall health care implications for simultaneous resections.

An MRI-Based Radiomic Prognostic Index Predicts Poor Outcome and Specific Genetic Alterations in Endometrial Cancer.

Integrative tumor characterization linking radiomic profiles to corresponding gene expression profiles has the potential to identify specific genetic alterations based on non-invasive radiomic profiling in cancer. The aim of this study was to develop and validate a radiomic prognostic index (RPI) based on preoperative magnetic resonance imaging (MRI) and assess possible associations between the RPI and gene expression profiles in endometrial cancer patients. Tumor texture features were extracted from preoperative 2D MRI in 177 endometrial cancer patients. The RPI was developed using least absolute shrinkage and selection operator (LASSO) Cox regression in a study cohort (n = 95) and validated in an MRI validation cohort (n = 82). Transcriptional alterations associated with the RPI were investigated in the study cohort. Potential prognostic markers were further explored for validation in an mRNA validation cohort (n = 161). The RPI included four tumor texture features, and a high RPI was significantly associated with poor disease-specific survival in both the study cohort (p < 0.001) and the MRI validation cohort (p = 0.030). The association between RPI and gene expression profiles revealed 46 significantly differentially expressed genes in patients with a high RPI versus a low RPI (p < 0.001). The most differentially expressed genes, COMP and DMBT1, were significantly associated with disease-specific survival in both the study cohort and the mRNA validation cohort. In conclusion, a high RPI score predicts poor outcome and is associated with specific gene expression profiles in endometrial cancer patients. The promising link between radiomic tumor profiles and molecular alterations may aid in developing refined prognostication and targeted treatment strategies in endometrial cancer.

Patient-derived organoids reflect the genetic profile of endometrial tumors and predict patient prognosis.

Background: A major hurdle in translational endometrial cancer (EC) research is the lack of robust preclinical models that capture both inter- and intra-tumor heterogeneity. This has hampered the development of new treatment strategies for people with EC. Methods: EC organoids were derived from resected patient tumor tissue and expanded in a chemically defined medium. Established EC organoids were orthotopically implanted into female NSG mice. Patient tissue and corresponding models were characterized by morphological evaluation, biomarker and gene expression and by whole exome sequencing. A gene signature was defined and its prognostic value was assessed in multiple EC cohorts using Mantel-Cox (log-rank) test. Response to carboplatin and/or paclitaxel was measured in vitro and evaluated in vivo. Statistical difference between groups was calculated using paired t-test. Results: We report EC organoids established from EC patient tissue, and orthotopic organoid-based patient-derived xenograft models (O-PDXs). The EC organoids and O-PDX models mimic the tissue architecture, protein biomarker expression and genetic profile of the original tissue. Organoids show heterogenous sensitivity to conventional chemotherapy, and drug response is reproduced in vivo. The relevance of these models is further supported by the identification of an organoid-derived prognostic gene signature. This signature is validated as prognostic both in our local patient cohorts and in the TCGA endometrial cancer cohort. Conclusions: We establish robust model systems that capture both the diversity of endometrial tumors and intra-tumor heterogeneity. These models are highly relevant preclinical tools for the elucidation of the molecular pathogenesis of EC and identification of potential treatment strategies.

Erratum: Author Correction: Patient-derived organoids reflect the genetic profile of endometrial tumors and predict patient prognosis.

[This corrects the article DOI: 10.1038/s43856-021-00019-x.].