Mesonephric-type adenocarcinomas of the ovary: prevalence, diagnostic reproducibility, outcome, and value of PAX2.

Mesonephric-type (or -like) adenocarcinomas (MAs) of the ovary are an uncommon and aggressive histotype. They appear to arise through transdifferentiation from Müllerian lesions creating diagnostic challenges. Thus, we aimed to develop a histologic and immunohistochemical (IHC) approach to optimize the identification of MA over its histologic mimics, such as ovarian endometrioid carcinoma (EC). First, we screened 1,537 ovarian epithelial neoplasms with a four-marker IHC panel of GATA3, TTF1, ER, and PR followed by a morphological review of EC to identify MA in retrospective cohorts. Interobserver reproducibility for the distinction of MA versus EC was assessed in 66 cases initially without and subsequently with IHC information (four-marker panel). Expression of PAX2, CD10, and calretinin was evaluated separately, and survival analyses were performed. We identified 23 MAs from which 22 were among 385 cases initially reported as EC (5.7%) and 1 as clear cell carcinoma. The interobserver reproducibility increased from fair to substantial (κ = 0.376-0.727) with the integration of the four-marker IHC panel. PAX2 was the single most sensitive and specific marker to distinguish MA from EC and could be used as a first-line marker together with ER/PR and GATA3/TTF1. Patients with MA had significantly increased risk of earlier death from disease (hazard ratio = 3.08; 95% CI, 1.62-5.85; p < 0.0001) compared with patients with EC, when adjusted for age, stage, and p53 status. A diagnosis of MA has prognostic implications for stage I disease, and due to the subtlety of morphological features in some tumors, a low threshold for ancillary testing is recommended.

Premature Classification of Early-stage Endometrioid Ovarian Carcinoma With Mesonephric-like Differentiation as Mesonephric-like Adenocarcinoma.

Ovarian mesonephric-like adenocarcinoma (MLA) is a rare tumor with potential origins in endometriosis and Müllerian-type epithelial tumors. The morphologic patterns of MLA overlap with those of endometrioid ovarian carcinoma (EnOC). We speculated that a subset of MLAs would be classified as EnOCs. In this study, we attempted to identify MLAs from malignant endometrioid tumors. Given that the study patients with MLAs had both endometrioid-like and mesonephric-like morphologies, we defined mesonephric-like differentiation (MLD) as an endometrioid tumor with focal or diffuse MLA morphology and immunophenotype. Twelve patients exhibited mesonephric-like morphologic patterns. Immunohistochemistry analysis for CD10, TTF-1, estrogen receptor (ER), GATA3, calretinin, and PAX8 expression was done using whole-section slides. Two patients without the MLA immunophenotype were excluded. Ten patients with EnOCs with MLD (8.3%) were identified from a cohort of 121 patients with malignant endometrioid tumors. All 10 patients were positive for TTF-1 and/or GATA3. Most patients were ER-negative. Morphologically, MLD was associated with papillary thyroid carcinoma-like nuclei, flattened cells, tubular, nested, reticular, or glomeruloid architecture, and infiltrative growth. All 10 patients had pre-existing endometriosis and/or adenofibromas. Among the EnOCs with MLD, 5 had coexisting components such as EnOC grade 1 [(G1), cases 4, 7, and 9], mucinous borderline tumor (case 1), and dedifferentiated carcinoma (case 10), with distinct borders between EnOC with MLD and the other components. Nine of the 10 MLA patients (90%) harbored KRAS hotspot mutations. In addition, 4 patients harboring other components shared common KRAS hotspot mutations. No significant prognostic differences were observed between patients with and without MLD. Based on our findings, we suggest that EnOC with MLD, especially in the early stages and without high-grade components, should be considered a subtype of EnOC. Overtreatment should be avoided in such patients, particularly in the early stages. In this study, as the characteristics between EnOC with MLD and MLA were not distinguishable, we considered both conditions to be on the same spectrum. EnOCs with MLD exhibit the MLA phenotype during disease progression and are prematurely classified as MLA. Nevertheless, more patients with EnOC who have MLD/MLA are required for a more robust comparison between conventional EnOC according to staging and grading.

Prediction of final pathology depending on preoperative myometrial invasion and grade assessment in low-risk endometrial cancer patients: A Korean Gynecologic Oncology Group ancillary study.

OBJECTIVES: Fertility-sparing treatment (FST) might be considered an option for reproductive patients with low-risk endometrial cancer (EC). On the other hand, the matching rates between preoperative assessment and postoperative pathology in low-risk EC patients are not high enough. We aimed to predict the postoperative pathology depending on preoperative myometrial invasion (MI) and grade in low-risk EC patients to help extend the current criteria for FST. METHODS/MATERIALS: This ancillary study (KGOG 2015S) of Korean Gynecologic Oncology Group 2015, a prospective, multicenter study included patients with no MI or MI <1/2 on preoperative MRI and endometrioid adenocarcinoma and grade 1 or 2 on endometrial biopsy. Among the eligible patients, Groups 1-4 were defined with no MI and grade 1, no MI and grade 2, MI <1/2 and grade 1, and MI <1/2 and grade 2, respectively. New prediction models using machine learning were developed. RESULTS: Among 251 eligible patients, Groups 1-4 included 106, 41, 74, and 30 patients, respectively. The new prediction models showed superior prediction values to those from conventional analysis. In the new prediction models, the best NPV, sensitivity, and AUC of preoperative each group to predict postoperative each group were as follows: 87.2%, 71.6%, and 0.732 (Group 1); 97.6%, 78.6%, and 0.656 (Group 2); 71.3%, 78.6% and 0.588 (Group 3); 91.8%, 64.9%, and 0.676% (Group 4). CONCLUSIONS: In low-risk EC patients, the prediction of postoperative pathology was ineffective, but the new prediction models provided a better prediction.

Endometroid type endometrial cancer after surgery: unravelling the interplay of sleep, fatigue, and psychological well-being.

BACKGROUND: Endometrioid carcinoma, originating in the endometrium glandular cells, is often detected early and treated by surgery. However, post-treatment life quality remains poorly studied, explicitly focusing on sleep quality, fatigue, and depression. METHODS: In this cross-sectional, observational study, 147 female patients with endometrioid-type endometrial carcinoma were evaluated using standardised tools-Pittsburgh Sleep Quality Index (PSQI), Fatigue Assessment Scale (FAS), and Beck Depression Inventory (BDI). Patients were categorised based on sleep quality and depression levels. The study employed correlation and regression analyses to examine the relationships among these variables. RESULTS: No correlations were found between sociodemographic or lifestyle variables and sleep quality, fatigue, or depression (P > 0.05). A strong correlation was identified between PSQI and FAS (r = 0.623; P < 0.001), PSQI and BDI (r = 0.291; P < 0.001), and FAS and BDI (r = 0.413; P < 0.001). Fatigue and tumour grade were potential predictors of poor sleep. Sleep quality and depression predicted fatigue, while only fatigue was a predictor for depression. Radiotherapy and external radiation rates were notably higher in the mild depression group. CONCLUSIONS: Our study suggests an imperative for integrated multi-disciplinary approaches that focus on medical and psychological aspects of patient care to enhance long-term well-being and quality of life.

Ovarian Metastasis from Human Papillomavirus-associated Usual-type Endocervical Adenocarcinoma: Clinicopathological Characteristics for Distinguishing from Primary Ovarian Mucinous or Endometrioid Tumor.

BACKGROUND/AIM: Distinguishing ovarian metastasis of usual-type endocervical adenocarcinoma (UEA) from primary ovarian tumors is often challenging because of several overlapping features. This study aimed to investigate the clinicopathological characteristics and outcomes of patients with metastatic ovarian UEA. PATIENTS AND METHODS: Clinicopathological information was collected from eight patients with metastatic ovarian UEA. Immunostaining was also performed. RESULTS: Most patients presented with adnexal masses that were suspected to be primary ovarian tumors. All examined cases showed block p16 positivity in paired primary and metastatic tumors. Five patients who completed post-operative chemotherapy or concurrent chemoradiotherapy (CCRT) did not experience recurrence. In contrast, one patient who refused further treatment after the first CCRT cycle experienced ovarian and peritoneal metastases. One patient with isolated ovarian metastasis left untreated and developed peritoneal metastasis during follow-up. CONCLUSION: Patients with UEA who received proper management for ovarian metastases showed favorable outcomes. Given that ovarian metastatic UEA can mimic primary ovarian borderline tumor or carcinoma of the mucinous or endometrioid type, pathologists should be aware of this unusual but distinctive morphology to avoid misdiagnosis and inappropriate treatment.

The survival benefit associated with complete macroscopic resection in epithelial ovarian cancer is histotype specific.

BACKGROUND: Complete macroscopic resection is a key factor associated with prolonged survival in ovarian cancer. However, most evidence derives from high-grade serous ovarian carcinoma, and the benefit of complete macroscopic resection in other histotypes is poorly characterized. We sought to determine which histotypes derive the greatest benefit from complete macroscopic resection to better inform future decisions on radical cytoreductive efforts. METHODS: We performed multivariable analysis of disease-specific survival across 2 independent patient cohorts to determine the magnitude of benefit associated with complete macroscopic resection within each histotype. RESULTS: Across both cohorts (Scottish: n = 1622; Surveillance, Epidemiology, and End Results [SEER]: n = 18 947), complete macroscopic resection was associated with prolonged disease-specific survival; this was more marked in the Scottish cohort (multivariable hazard ratio [HR] = 0.44, 95% confidence interval [CI] = 0.37 to 0.52 vs HR = 0.59, 95% CI = 0.57 to 0.62 in SEER). In both cohorts, clear cell ovarian carcinoma was among the histotypes to benefit most from complete macroscopic resection (multivariable HR = 0.23 and HR = 0.50 in Scottish and SEER cohorts, respectively); high-grade serous ovarian carcinoma patients demonstrated highly statistically significant and clinically meaningful survival benefit, but this was of lower magnitude than in clear cell ovarian carcinoma and endometrioid ovarian carcinoma across both cohorts. The benefit derived in low-grade serous ovarian carcinoma is also high (multivariable HR = 0.27 in Scottish cohort). Complete macroscopic resection was associated with prolonged survival in mucinous ovarian carcinoma patients in the SEER cohort (multivariable HR = 0.65), but the association failed to reach statistical significance in the Scottish cohort. CONCLUSIONS: The overall ovarian cancer patient population demonstrates clinically significant survival benefit associated with complete macroscopic resection; however, the magnitude of benefit differs between histotypes.

Correlation between immunohistochemical staining and clinicopathological findings in endometrial carcinoma.

OBJECTIVES: To analyze the immunohistochemical staining pattern of mismatch repair (MMR) proteins and p53 in endometrial carcinoma cases, including different subtypes and stages, to gain insights into their role in the pathogenesis and clinical behaviour of this malignancy. METHODS: In this study, we investigate the association between MMR deficiency, p53 mutational status, and clinical outcomes in various subtypes of endometrial carcinoma. The immunohistochemical staining pattern of MMR proteins in 96 cases of endometrial carcinoma have been analyzed, including 72 endometrioid, 14 papillary serous, 5 clear cell, and 5 mixed Müllerian tumor. RESULTS: The results showed that 36 cases were MMR deficient, with the majority being of endometrioid subtype. The p53 immunostain showed a mutational pattern in a subset of cases, with a documented dismal prognosis. However, aforementioned stains failed to predict synchronous or metachronous cancers in 5 patients. CONCLUSION: These findings highlight the importance of MMR and p53 immunohistochemical staining in the classification, and prognosis of endometrial carcinoma.

Synchronous Well-Differentiated Papillary Mesothelioma and Endometrioid Adenocarcinoma Arising From Endometriosis.

Well-differentiated papillary mesothelioma (WDPM) is a rare mesothelial tumor of uncertain malignant potential. We present a unique case of a woman with synchronous WDPM and well-differentiated endometrioid adenocarcinoma (EA) arising from extraovarian endometriosis. A 56-year-old postmenopausal woman presented with a several-month history of right lower quadrant abdominal pain. She had a history of supracervical hysterectomy and bilateral salpingo-oophorectomy secondary to endometriosis. Imaging reported a mass in the right lower quadrant originating from the distal ileum. At laparotomy, the patient underwent a right colectomy with resection of the terminal ileum and excision of a solitary peritoneal nodule. Pathology was consistent with a diagnosis of well-differentiated EA (arising from extraovarian endometriosis) and WDPM. Further treatment consisted of complete surgical staging/debulking and adjuvant chemotherapy directed toward metastatic well-differentiated EA. Surgeons should be familiar with WDPM as a potential finding in women of reproductive age undergoing abdominal surgery for any indication.

Trends in incidence and hormonal management of endometrial cancer during potentially reproductive age in Japan: a population-based study.

BACKGROUND: We aimed to investigate the trends in the incidence and treatment of endometrial cancer (EC) during potentially reproductive age in Japan, with a special focus on the relative oncologic safety of hormonal therapy (HT) over surgery. METHODS: This population-based retrospective cohort study was conducted using data from the Osaka Cancer Registry from 2004 to 2018. Women with EC were first identified and then distributions of age, stage, histology, and initial treatment were examined. Then, the relative oncologic safety of HT over surgery in patients under the age of 50 years was evaluated. RESULTS: Among the 9417 patients with EC, 1937 were diagnosed during their potentially reproductive age (< 50 years). The incidence of EC during potentially reproductive age has increased from 18.5% in 2004-2011 to 21.9% in 2012-2018. ECs during potentially reproductive age more frequently displayed favorable characteristics, such as endometrioid histology, and lower histological grade than those in non-potentially reproductive age. Among the 1223 patients diagnosed with localized endometrioid EC, 74 cases (6.0%) received HT as an initial treatment, while 1100 cases (90.0%) underwent surgery as their initial treatment. When the two treatment groups were compared, there was no significant difference in overall survival (p = 0.3713). The estimated 5-year survival rates were 100 and 98.8% in the HT and surgery groups, respectively. CONCLUSION: EC is increasingly diagnosed during potentially reproductive age in Japan. The use of HT as an initial treatment is increasing, and achieved comparable survival outcomes to urgery against localized endometrioid EC during the potentially reproductive age.

Molecular Classification Outperforms Histologic Classification in Prognostication of High-grade Endometrial Carcinomas With Undifferentiated and Sarcomatous Components.

Since the establishment of 4 molecular subgroups of endometrial carcinoma (EC), there has been significant interest in understanding molecular classification in the context of histologic features and diagnoses. ECs with undifferentiated, spindle, and/or sarcomatous components represent a diagnostically challenging subset of tumors with overlapping clinical and histologic features. We examined the clinicopathologic, morphologic, immunohistochemical, and molecular features of these tumors identified in our institutions' pathology databases using immunohistochemistry and targeted sequencing. Disease-specific survival (DSS) and progression-free survival (PFS) were analyzed using Kaplan-Meier curves and log-rank tests. One hundred sixty-two ECs were included: carcinosarcomas (UCS; n=96), dedifferentiated/undifferentiated EC (DDEC/UDEC; n=49), and grade 3 endometrioid EC with spindled growth (GR3spEEC) (n=17). All molecular subgroups were represented in all histologic subtypes and included 12 (7%) POLE -mutated ( POLE mut), 43 (27%) mismatch repair-deficient (MMRd), 77 (48%) p53-abnormal (p53abn), and 30 (19%) no specific molecular profile (NSMP) tumors. However, the molecular classification (irrespective of histologic diagnosis) was a significant predictor for both DSS ( P =0.008) and P≤0.0001). POLE mut EC showed an excellent prognosis with no recurrences or deaths from the disease. MMRd tumors also showed better outcomes relative to NSMP and p53abn tumors. In conclusion, molecular classification provides better prognostic information than histologic diagnosis for high-grade EC with undifferentiated and sarcomatous components. Our study strongly supports routine molecular classification of these tumors, with emphasis on molecular group, rather than histologic subtyping, in providing prognostication.

Preoperative cancer antigen-125 levels as a predictor of recurrence in early-stage endometrial cancer.

OBJECTIVE: Endometrial cancer is the most common gynecological cancer in developed countries, with a majority of cases being low-grade endometrioid endometrial cancer. Identifying risk factors for disease recurrence and poor prognosis is critical. This study aimed to assess the correlation between preoperative cancer antigen-125 levels and disease recurrence in early-stage endometrioid endometrial cancer patients. METHODS: The study was a retrospective analysis of 217 patients diagnosed with endometrioid endometrial cancer who underwent surgical treatment at a university-affiliated tertiary hospital between 2016 and 2022. Patients were divided into two groups based on their preoperative cancer antigen-125 levels and compared with clinicopathological findings and disease recurrence. Disease-free survival rates were calculated, and logistic regression analysis was performed to determine independent factors affecting disease-free survival. RESULTS: The mean age of patients was 61.59±0.75 years, and the mean follow-up time was 36.95±1.18 months. The mean cancer antigen-125 level was 27.80±37.81 IU/mL. The recurrence rate was significantly higher in the group with elevated cancer antigen-125 levels (p=0.025). Disease-free survival was lower in patients with elevated cancer antigen-125 compared with those with normal levels (p=0.005). Logistic regression analysis revealed that elevated cancer antigen-125 levels were associated with disease recurrence (OR: 3.43, 95%CI 1.13-10.37, p=0.029). CONCLUSION: The findings of this study suggest that preoperative cancer antigen-125 levels can be used as a predictor of disease recurrence in early-stage endometrioid endometrial cancer patients. cancer antigen-125 levels may be a useful tool for risk stratification and patient management in endometrial cancer.

Global Incidence of Ovarian Cancer According to Histologic Subtype: A Population-Based Cancer Registry Study.

PURPOSE: Ovarian cancer can be categorized into distinct histologic subtypes with varying identifiable risk factors, molecular composition, clinical features, and treatment. The global incidence of ovarian cancer subtypes remains limited, especially in low- and middle-income countries (LMICs) without high-quality cancer registry systems. MATERIALS AND METHODS: We used data from population-based cancer registries of the Cancer Incidence in Five Continents project to calculate the proportions of serous, mucinous, endometrioid, clear cell, and other histologic subtypes of ovarian cancer. Proportions were applied to the estimated numbers of patients with ovarian cancer from Global Cancer Observatory 2020. Age-standardized incidence rates were calculated. RESULTS: Globally, an estimated 133,818 new patients of serous cancer, 35,712 new patients of mucinous cancer, 29,319 new patients of endometrioid cancer, and 17,894 new patients of clear cell cancer were identified in 2020. The distribution of ovarian cancer histologic subtypes exhibited regional variation. Eastern Europe had the highest rate of serous and mucinous carcinomas, whereas Northern Africa and Eastern Asia had the highest burden of endometrioid and clear cell carcinomas, respectively. CONCLUSION: This study provides a global incidence landscape of histologic subtypes of ovarian cancer, particularly in LMICs lacking comprehensive registry systems. Our analysis offers valuable insights into disease burden and guidance for tailored strategies for prevention of ovarian cancer.

Validating the 2023 FIGO staging system: A nomogram for endometrioid endometrial cancer and adenocarcinoma.

BACKGROUND: To find the factors impacting overall survival (OS) prognosis in patients with endometrioid endometrial carcinoma (EEC) and adenocarcinoma and to establish a nomogram model to validate the 2023 International Federation of Obstetrics and Gynecology (FIGO) staging system for endometrial cancer. METHODS: Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) training cohort. An independent validation cohort was obtained from the First Affiliated Hospital of Anhui Medical University between 2008 and 2023. Cox regression analysis identified independent prognostic factors for OS in EEC and adenocarcinoma patients. A nomogram predicting OS was developed and validated utilizing the C-index, calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). The relationship between the tumor grade and prognosis of EEC and adenocarcinoma was quantified using net reclassification improvement (NRI), propensity score matching (PSM), and Kaplan-Meier curves. RESULTS: Cox regression analysis identified age, race, marital status, tumor grade, tumor stage, tumor size, and chemotherapy as independent prognostic factors for OS. A nomogram for predicting OS was developed based on these factors. The C-indexes for the OS nomogram was 0.743 and 0.720 for the SEER training set and external validation set, respectively. The area under the ROC (AUC) for the OS nomogram was 0.755, 0.757, and 0.741 for the SEER data subsets and 0.844, 0.719, and 0.743 for the external validation subsets. Calibration plots showed high concordance between the nomogram-predicted and observed OS. DCA also demonstrated the clinical utility of the OS nomogram. NRI, PSM, and survival analyses revealed that tumor grade was the most important histopathological factor for EEC and adenocarcinoma prognosis. CONCLUSION: Seven independent prognostic variables for the OS of patients with EEC and adenocarcinoma were identified. The established OS nomogram has good predictive ability and clinical utility and validates the 2023 endometrial cancer FIGO staging system.

Assessment of the localization of chondroitin sulfate in various types of endometrial carcinoma.

INTRODUCTION: This study aimed to assess the localization of chondroitin sulfate (CS), a primary extracellular matrix component, in the stromal region of endometrial carcinoma (EC). METHODS: Immunostaining was performed on 26 endometrial endometrioid carcinoma (EEC) samples of different grades and 10 endometrial serous carcinoma (ESC) samples to evaluate CS localization. This was further confirmed by Alcian Blue (AB) staining as well. RESULTS: In the G1-EEC samples, CS showed reactivity with fibrovascular stroma, supporting closely packed glandular crowding and papillary structures. As the grade increased, the original interstitial structure was re-established, and the localization of CS in the perigulandular region decreased. In the ESC samples, the thick fibrous strands supporting the papillary architecture showed reactivity with CS; however, the delicate stromal region branching into the narrow region showed poor reactivity. The AB staining results showed similar characteristics to the immunostaining ones. CONCLUSIONS: The characteristic localization of CS in various EC types was elucidated. The present study provides new information on endometrial stromal assessment.

Genetic and epigenetic alterations in precursor lesions of endometrial endometrioid carcinoma.

The hyperplasia-carcinoma sequence is a stepwise tumourigenic programme towards endometrial cancer in which normal endometrial epithelium becomes neoplastic through non-atypical endometrial hyperplasia (NAEH) and atypical endometrial hyperplasia (AEH), under the influence of unopposed oestrogen. NAEH and AEH are known to exhibit polyclonal and monoclonal cell growth, respectively; yet, aside from focal PTEN protein loss, the genetic and epigenetic alterations that occur during the cellular transition remain largely unknown. We sought to explore the potential molecular mechanisms that promote the NAEH-AEH transition and identify molecular markers that could help to differentiate between these two states. We conducted target-panel sequencing on the coding exons of 596 genes, including 96 endometrial cancer driver genes, and DNA methylome microarrays for 48 NAEH and 44 AEH lesions that were separately collected via macro- or micro-dissection from the endometrial tissues of 30 cases. Sequencing analyses revealed acquisition of the PTEN mutation and the clonal expansion of tumour cells in AEH samples. Further, across the transition, alterations to the DNA methylome were characterised by hypermethylation of promoter/enhancer regions and CpG islands, as well as hypo- and hyper-methylation of DNA-binding regions for transcription factors relevant to endometrial cell differentiation and/or tumourigenesis, including FOXA2, SOX17, and HAND2. The identified DNA methylation signature distinguishing NAEH and AEH lesions was reproducible in a validation cohort with modest discriminative capability. These findings not only support the concept that the transition from NAEH to AEH is an essential step within neoplastic cell transformation of endometrial epithelium but also provide deep insight into the molecular mechanism of the tumourigenic programme. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Tailoring postoperative management through sentinel lymph node biopsy in low- and intermediate-risk endometrial cancer - the SENTRY clinical trial.

BACKGROUND: While total hysterectomy and bilateral salpingo-oophorectomy without lymph node staging are standard for low- and intermediate-risk endometrial cancer, certain histopathologic factors revealed after surgery can necessitate additional interventions. Our study assessed the influence of sentinel lymph node biopsy on postoperative decision-making. MATERIALS AND METHODS: In the SENTRY trial (July 2021 - February 2023), we enrolled patients with International Federation of Gynaecology and Obstetrics (FIGO) stage IA-IB low-grade endometrioid endometrial cancer. Laparoscopic sentinel lymph node mapping using indocyanine green was performed alongside total hysterectomy with bilateral salpingo-oophorectomy. Subsequent management changes based on sentinel lymph node biopsy results were evaluated. The trial was registered at ClinicalTrials.gov (NCT04972682). RESULTS: Of the 100 enrolled participants, a bilateral detection rate of 91% was observed with a median detection time of 10 min (interquartile range 8-13 min). Sentinel lymph node metastases were found in 8% (N = 8) of participants. Postoperative FIGO staging increased in 15% (N = 15) and decreased in 5% (N = 5) of patients. Sentinel lymph node biopsy results altered the adjuvant treatment plan for 20% (N = 20): external beam radiotherapy was omitted in 12% (N = 12) while 6% (N = 6) had external beam radiotherapy +/- systemic chemotherapy added due to sentinel lymph node metastases. In 2% (N = 2), the external beam radiotherapy field was expanded with the paraaortic region. No intraoperative complications were reported and no 30-day major morbidity and mortality occurred. Throughout a median follow-up of 14 (95% CI 12-15 months, neither patient-reported lymphedema nor pelvic recurrence surfaced in the cohort. CONCLUSIONS: Sentinel lymph node biopsy using indocyanine green is a safe procedure and allows tailoring adjuvant therapy in presumed low- and intermediate-risk endometrial cancer. It assists in avoiding external beam radiotherapy overtreatment and introducing additional modalities when necessary.

Endometrial carcinoma: 10 years of TCGA (the cancer genome atlas): A critical reappraisal with comments on FIGO 2023 staging.

The Cancer Genome Atlas (TCGA) Research Network described 4 molecular subgroups of endometrial carcinomas with different outcome: 1) POLE ultramutated endometrioid carcinomas which have an indolent behavior; 2) microsatellite instability hypermutated endometrioid carcinomas associated with intermediate prognosis; 3) copy-number low endometrioid carcinomas also with intermediate prognosis; and 4) copy-number high predominantly serous (non-endometrioid) but also serous-like endometrioid carcinomas, almost always carrying TP53 mutations, with poor clinical outcome. After 10 years of comprehensive analysis, it appears that the only real contribution of TCGA to the clinical management of these patients would be limited to the infrequent high-grade, early-stage endometrioid carcinomas with POLE exonuclease domain mutations, as these patients could benefit from a de-escalating treatment; knowledge about the other three subgroups has not changed significantly. The copy-number low (or non-specific genetic profile) which is the most frequent subgroup, is a mixture subgroup where investigators are currently trying to establish prognostic markers; for example, unexpected variations in a relatively small percentage of cases (i.e., CTNNB1 mutated or p53 aberrant low-grade and low-stage endometrioid carcinomas associated with unfavorable prognosis). On the other hand, TCGA has underlined that a small number of grade 3 endometrioid carcinomas, all TP53 mutated, overlap with copy-number high serous carcinomas. Recently, TCGA molecular subgroups have been integrated into the 2023 International Federation of Gynecology and Obstetrics (FIGO) staging classification which incorporates other non-anatomic parameters like histotype, tumor grade, and lymphovascular space invasion. The result is a complicated and non-intuitive classification that makes its clinical application difficult and does not facilitate correspondence with the 2009 FIGO staging.

Endometrioid Endometrial RNA Index Predicts Recurrence in Stage I Patients.

PURPOSE: Risk prediction with genomic and transcriptomic data has the potential to improve patient outcomes by enabling clinicians to identify patients requiring adjuvant treatment approaches, while sparing low-risk patients from unnecessary interventions. Endometrioid endometrial carcinoma (EEC) is the most common cancer in women in developed countries, and rates of endometrial cancer are increasing. EXPERIMENTAL DESIGN: We collected a 105-patient case-control cohort of stage I EEC comprising 45 patients who experienced recurrence less than 6 years after excision, and 60 Fédération Internationale de Gynécologie et d'Obstétrique grade-matched controls without recurrence. We first utilized two RNA-based, previously validated machine learning approaches, namely, EcoTyper and Complexity Index in Sarcoma (CINSARC). We developed Endometrioid Endometrial RNA Index (EERI), which uses RNA expression data from 46 genes to generate a personalized risk score for each patient. EERI was trained on our 105-patient cohort and tested on a publicly available cohort of 263 patients with stage I EEC. RESULTS: EERI was able to predict recurrences with 94% accuracy in the training set and 81% accuracy in the test set. In the test set, patients assigned as EERI high-risk were significantly more likely to experience recurrence (30%) than the EERI low-risk group (1%) with a hazard ratio of 9.9 (95% CI, 4.1-23.8; P < 0.001). CONCLUSIONS: Tumors with high-risk genetic features may require additional treatment or closer monitoring and are not readily identified using traditional clinicopathologic and molecular features. EERI performs with high sensitivity and modest specificity, which may benefit from further optimization and validation in larger independent cohorts.

Endometrial Cancer in a Family With RAD51D Gene Mutation.

RAD51 complex plays an important role in homologous recombination deficiency and germline mutations have a well-documented association with breast and tubo-ovarian carcinoma, as well as serous-type endometrial carcinoma. We report a family of French Canadian ancestry with a germline mutation in RAD51D and two sisters presenting with endometrial carcinoma, endometrioid-type. The risk factors for endometrial adenocarcinoma, endometrioid-type are discussed in the context of the RAD51-associated carcinomas described to date.

Proteogenomic insights into early-onset endometrioid endometrial carcinoma: predictors for fertility-sparing therapy response.

Endometrial carcinoma remains a public health concern with a growing incidence, particularly in younger women. Preserving fertility is a crucial consideration in the management of early-onset endometrioid endometrial carcinoma (EEEC), particularly in patients under 40 who maintain both reproductive desire and capacity. To illuminate the molecular characteristics of EEEC, we undertook a large-scale multi-omics study of 215 patients with endometrial carcinoma, including 81 with EEEC. We reveal an unexpected association between exposome-related mutational signature and EEEC, characterized by specific CTNNB1 and SIGLEC10 hotspot mutations and disruption of downstream pathways. Interestingly, SIGLEC10Q144K mutation in EEECs resulted in aberrant SIGLEC-10 protein expression and promoted progestin resistance by interacting with estrogen receptor alpha. We also identified potential protein biomarkers for progestin response in fertility-sparing treatment for EEEC. Collectively, our study establishes a proteogenomic resource of EEECs, uncovering the interactions between exposome and genomic susceptibilities that contribute to the development of primary prevention and early detection strategies for EEECs.