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.

Investigating the Spatial Distribution of Proliferating Cells in Primary Ovarian Cancers.

BACKGROUND: Ovarian cancer (OC) accounts for about 4% of female cancers globally. While Ki67-immunopositive (Ki67+) cell density is commonly used to assess proliferation in OC, the two-dimensional (2D) distribution pattern of these cells is poorly understood. This study explores the 2D distribution pattern of Ki67+ cells in primary OC tissues and models the proliferation process to improve our understanding of this hallmark of cancer. METHODS: A total of 100 tissue cores, included in a tissue microarray (TMA) representing 5 clear cell carcinomas, 62 serous carcinomas, 10 mucinous adenocarcinomas, 3 endometrioid adenocarcinomas, 10 lymph node metastases from OC, and 10 samples of adjacent normal ovary tissue, were stained using a standardized immunohistochemical protocol. The computer-aided image analysis system assessed the 2D distribution pattern of Ki67+ proliferating cells, providing the cell number and density, patterns of randomness, and cell-to-cell closeness. Three computer models were created to simulate behavior and responses, aiming to gain insights into the variations in the proliferation process. RESULTS: Significant differences in Ki67+ cell density were found between low- and high-grade serous carcinoma/mucinous adenocarcinomas (p = 0.003 and p = 0.01, respectively). The Nearest Neighbor Index of Ki67+ cells differed significantly between high-grade serous carcinomas and endometrioid adenocarcinomas (p = 0.01), indicating distinct 2D Ki67+ distribution patterns. Proxemics analysis revealed significant differences in Ki67+ cell-to-cell closeness between low- and high-grade serous carcinomas (p = 0.002). Computer models showed varied effects on the overall organization of Ki67+ cells and the ability to preserve the original 2D distribution pattern when altering the location and/or density of Ki67+ cells. CONCLUSIONS: Cell proliferation is a hallmark of OCs. This study provides new evidence that investigating the Ki67+ cell density and 2D distribution pattern can assist in understanding the proliferation status of OCs. Moreover, our computer models suggest that changes in Ki67+ cell density and their location are critical for maintaining the 2D distribution pattern.

Prognostic evaluation of lymph-vascular space invasion in patients with endometrioid and non-endometrioid endometrial cancer: A multicenter study.

INTRODUCTION: The prognostic value of lymph-vascular space invasion (LVSI) on endometrial cancer (EC) remains controversial. This study aimed to explore the impact of LVSI on patients with endometrioid and non-endometrioid EC in China. MATERIALS AND METHODS: We analyzed EC patients who underwent surgery from 2010 to 2019 in seven Chinese hospitals retrospectively and stratified patients based on histopathologic types and LVSI status. Endpoints were disease-free survival (DFS) and overall survival (OS). Propensity score matching (PSM) algorithm was used to balance the confounding factors. The survival was examined using Kaplan-Meier analysis. Cox proportional hazards regression analyses were used to find prognostic independent risk factors. RESULTS: Among 3715 EC patients, LVSI positive rate was 9.31% (346/3715). After matching, LVSI present group had shorter DFS (P = 0.005), and similar OS (P = 0.656) than LVSI absent group for endometrioid EC patients. For non-endometrioid EC patients, there was no statistical difference in either DFS (P = 0.536) or OS (P = 0.512) after matching. The multivariate Cox analysis showed that LVSI was an independent risk factor of DFS [hazard ratio (HR) 2.62, 95% confidence intervals (CI) 1.35-5.10, P = 0.005] and not OS (HR 1.24, 95%CI 0.49-3.13, P = 0.656) for endometrioid EC patients. It was not a prognostic factor of either DFS (HR 1.28, 95%CI 0.58-2.81, P = 0.539) or OS (HR 1.33, 95%CI 0.55-3.13, P = 0.515) for non-endometrioid EC patients. CONCLUSION: LVSI is an adverse prognostic factor for endometrioid EC patients and has no impact on non-endometrioid EC patients. Necessity of postoperative adjuvant therapy based on LVSI needs to be carefully considered for non-endometrioid EC patients.

The analysis of preoperative or intraoperative factors in predicting the escalation of surgical pathological staging of patients with clinical stage I endometrioid carcinoma: A retrospective clinical study.

To retrospectively analyze the preoperative and intraoperative influencing factors in predicting the escalation of surgical pathological staging in patients with clinical stage I endometrioid carcinoma. Patients with clinical stage I endometrioid carcinoma at Women's Hospital, School of Medicine, Zhejiang University, between January 2002 and December 2015 were enrolled in this study. Due to preoperative or intraoperative surgical exploration, the patients with one or more preoperative or intraoperative high-risk factors underwent total hysterectomy, bilateral salpingo-oophorectomy and lymphadenectomy, totaling 535 cases. The preoperative and intraoperative influencing factors that could lead to the escalation of postoperative surgical pathological staging were further analyzed. 1. There were 535 patients diagnosed with clinical stage I endometrioid carcinoma before surgery, 125 patients were upgraded with postoperative pathological staging, for a rate of 23.36%. 2. Kaplan-Meier survival curve analysis showed that the prognosis in postoperative surgical pathological staging upgraded cases was worse than that in nonupgraded cases. The tumor-free survival and overall survival rates in the 2 groups were significantly different (P < .001). 3. Univariate analysis showed that preoperative degree of myometrial infiltration, intraoperative visual myometrial infiltration depth, massive size of tumor (diameter ≥ 4 cm) and preoperative abnormal serum cancer antigen 125 (CA125) level were associated with the escalation of surgical pathological staging (P < .05). Multivariate analysis indicated that massive size of tumor and preoperative serum abnormal CA125 level were independent predictors of whether postoperative pathological staging would be upgraded (P < .05). 4. The receiver operating characteristic curve drawn with the massive size of tumor and/or the preoperative serum CA125 level abnormality could be used to predict the probability of postoperative pathological upstaging. The results showed that the area from the combination of the 2 factors under the receiver operating characteristic curve was 0.723 (95% confidence interval, 0.672-0.773), suggesting that the combination of massive size of tumor and abnormal preoperative serum CA125 level may serve as an influencing factor for predicting the postoperative pathological staging upgrades. The clinical stage I endometrioid carcinoma patients with massive size of tumor and abnormal preoperative serum CA125 level need to be fully evaluated to ensure appropriate management as soon as possible, since they are more likely to experience postoperative pathological staging upgrades.

Accuracy of endometrial sampling in the diagnosis of endometrial cancer: a multicenter retrospective analysis of the JAGO-NOGGO.

BACKGROUND: Accurate preoperative molecular and histological risk stratification is essential for effective treatment planning in endometrial cancer. However, inconsistencies between pre- and postoperative tumor histology have been reported in previous studies. To address this issue and identify risk factors related to inaccurate histologic diagnosis after preoperative endometrial evaluation, we conducted this retrospective analysis. METHODS: We conducted a retrospective analysis involving 375 patients treated for primary endometrial cancer in five different gynaecological departments in Germany. Histological assessments of curettage and hysterectomy specimens were collected and evaluated. RESULTS: Preoperative histologic subtype was confirmed in 89.5% of cases and preoperative tumor grading in 75.2% of cases. Higher rates of histologic subtype variations (36.84%) were observed for non-endometrioid carcinomas. Non-endometrioid (OR 4.41) histology and high-grade (OR 8.37) carcinomas were identified as predictors of diverging histologic subtypes, while intermediate (OR 5.04) and high grading (OR 3.94) predicted diverging tumor grading. CONCLUSION: When planning therapy for endometrial cancer, the limited accuracy of endometrial sampling, especially in case of non-endometrioid histology or high tumor grading, should be carefully considered.

Characteristics of patients with late recurrence endometrial cancer.

AIM: We planned this study to assess endometrial cancer (EC) patients who had late metastasis. MATERIALS AND METHODS: This retrospective study constituted a review of the records of patients who were diagnosed with EC and underwent hysterectomy at the Gynecologic Oncology Clinic between 1996 and 2018. Relapses occurring after the first three years following primary treatment of EC are considered late recurrences. Post-relapse survival (PRS) refers to the time to the last follow-up or the patient's death after relapse. RESULTS: Late metastases were identified in 42 patients, 20 (47.6%) of whom had locoregional recurrence and 22 of whom (52.4%) had extrapelvic recurrence. Median disease-free survival (DFS) times were 61 (range: 43-78) and 65 (range: 48-81) months for the groups with locoregional and extrapelvic recurrences, respectively (P = 0.462). The 5-year PRS rate for the patients was 61.1%, with 63.8% having locoregional and 59.4% having extrapelvic late metastasis (P = 0.969). CONCLUSION: Among the patients with late metastases, those with endometrioid type EC were found to have a better prognosis. It has been shown that locoregional or extrapelvic organ recurrence does not significantly affect survival in patients with late relapse. Although our results are not statistically significant for cases of locoregional late metastases, surgical resection increases survival rates.

The Role of Lymphovascular Space Invasion and Cytology in the Prognosis of Endometrial Cancer.

BACKGROUND: Lymphovascular space invasion (LVSI) and cytology are both independent and strong prognostic factors in endometrial cancer. This study aims to highlight the impact of LVSI and cytology positivity on prognosis, in addition to molecular classification. METHODS: A retrospective review was conducted on the records of 223 patients with endometrial cancer diagnosed between January 2011 and January 2021. The inclusion criteria stipulated that the patients were diagnosed with endometrial cancer by endometrial biopsy and were operated in the clinic. The exclusion criteria included sarcoma in the postoperative pathology report results or synchronous tumor. Staging was performed according to the Fédération internationale de gynécologie et d'obstétrique (FIGO) 2009 criteria. Cytology (using 50 cc saline) was obtained upon entry into the peritoneal cavity. In 20 patients, saline was not used due to the presence of ascites in the abdomen. The Kaplan-Meier method was employed to evaluate overall survival and progression-free survival. Survival rates were compared in terms of cytology and LVSI. RESULTS: After analyzing the postoperative pathology results, it was found that the mean tumor size was 4.03 ± 2.3 cm. The most common histological type was endometrioid carcinoma, with stage IA being the most common stage. Out of 223 patients with endometrial cancer, the overall survival rate was 82.4%, and the progression-free survival rate was 88.3%. For patients negative for LVSI, the progression-free survival rate was 93%, while for LVSI-positive patients, it was 77.3% (p < 0.001). Additionally, the progression-free survival rate for patients negative for cytology was 90.4%, whereas for cytology-positive patients, it was 77.1% (p < 0.05). CONCLUSIONS: In our study, we observed that LVSI positivity and cytology positivity also reduced the overall survival rate. We aimed to highlight that, in addition to molecular classification, cytology positivity and LVSI positivity are still highly significant and independent factors in prognosis.

Trichorhinophalangeal Syndrome Type 1 Immunohistochemical Expression in Carcinomas of Gynecologic Origin.

Trichorhinophalangeal syndrome type 1 (TRPS1) is a new reportedly sensitive and specific immunohistochemical marker for carcinomas of breast origin, including triple-negative (estrogen receptor, progesterone receptor, and HER2) tumors. In our practice, we have observed a subset of cases of nonmammary carcinomas that are positive for TRPS1, with higher frequency in cytology effusion samples with metastatic gynecologic malignancies. This study aimed to evaluate the expression of TRPS1 in a large tissue cohort of Müllerian carcinomas. We retrospectively retrieved 105 cases of formalin-fixed paraffin-embedded gynecologic tumors from our surgical pathology archives. Cases corresponded to tumors of tubo-ovarian (17 high-grade serous carcinomas, 3 low-grade serous carcinomas, 2 clear cell carcinomas, and 8 endometrioid adenocarcinomas), endometrial (25 endometrioid adenocarcinomas, 8 serous carcinomas, 6 clear cell carcinomas, 12 carcinosarcomas, 1 dedifferentiated carcinoma, and 1 mesonephric-like adenocarcinoma), cervical (6 human papillomavirus [HPV]-associated squamous cell carcinomas [SCCs], 11 HPV-associated endocervical adenocarcinomas, and 2 HPV-independent gastric-type endocervical adenocarcinomas), and vulvar (2 HPV-independent SCCs and 1 HPV-associated SCC) origins. Immunohistochemistry for TRPS1 was performed in whole tissue sections and assessed for positivity (≥5% of nuclear labeling), distribution (focal: 5% to 49%, diffuse: 50% to 100%), and intensity (1+, 2+, 3+) in tumor cells. Positive TRPS1 staining was observed in 51.4% (54/105) of cases. Most tumors (64.8%) demonstrated diffuse labeling, while focal in 35.2%. Among positive cases, the intensity was predominantly 1+ (57.4%), followed by 2+ (33.3%) and 3+ (9.2%). Tumors with a high percentage of positivity overall consisted of tubo-ovarian (70%) and endometrial carcinomas (58.4%). TRPS1 immunostain is often expressed in gynecologic carcinomas. Awareness of this phenomenon is crucial when evaluating challenging cases in which the differential diagnosis includes a malignancy of breast origin, to avoid misclassification of the primary site.

Evaluating the Prognostic Factors and Survival Rates of Endometrial Cancer Patients in a Tertiary Referral Hospital in Northeast Thailand.

OBJECTIVES: This study aims to determine the 5-year and 10-year overall survival rates, mortality incidence, median survival time, and factors influencing the survival of endometrial cancer (EC) patients' post-diagnosis at the largest hospital in northeast Thailand. We particularly focus on the impact of access to health insurance schemes. METHODS: We conducted a retrospective analysis of data from EC patients admitted to Srinagarind Hospital between 2010 and 2019. Overall survival was estimated using the Kaplan-Meier method. Multivariate Cox regression analysis identified factors associated with survival, with results expressed as adjusted hazard ratios (AHR) and 95% confidence intervals (CI). RESULTS: Among the 673 patients, the 5-year overall survival rate stood at 76.43% (95% CI: 72.72-79.70), and the 10-year rate at 67.86% (95% CI: 62.98-72.25). Notably, advanced age (≥60 years), stage III and IV cancer, and non-endometrioid histopathology were found to significantly increase post-diagnosis mortality risk (AHR = 2.39, 3.13, 4.62; 95% CI: 1.03-5.53, 2.07-4.74, 2.66-8.04; p-value <0.05, <0.001, <0.001). Surprisingly, we observed no significant correlation between health insurance schemes and mortality risk, suggesting that different insurance programs did not significantly affect EC patient survival in this study. CONCLUSION: health insurance schemes had no significant impact on endometrial cancer patient outcomes in Thailand, likely due to comprehensive coverage. Treatment modalities, notably surgery, showed no statistically significant differences, possibly due to early diagnosis. High-risk groups may benefit from adjuvant therapy. Early surgical intervention is crucial, with its association with disease stage emphasized. These findings inform cancer care decisions and healthcare policy development.
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Low-grade endometrioid endometrial cancer with adnexal only metastasis: Evaluation of de-escalation of adjuvant therapy.

OBJECTIVE: To assess survival outcomes of stage IA3 endometrial cancer and the association of adjuvant therapy and survival. METHODS: The National Cancer Database was retrospectively queried to examine 594 and 1455 patients with stage IA3 and IIIA1 endometrial cancer, respectively, from 2010-2015. Overall survival (OS) was examined based on adjuvant therapy: multimodal combination chemotherapy and external beam radiotherapy, chemotherapy alone, external beam radiotherapy alone, and none. RESULTS: For stage IA3 disease, 109 (18.4%) patients did not receive adjuvant therapy. The 5-year OS rates for the no adjuvant therapy group and the combination group were 86.3% and 91.4%, respectively (adjusted-hazard ratio [aHR] 1.23, 95% confidence interval [CI] 0.70-2.18). This survival association was consistent when compared to chemotherapy alone (5-year OS rates 86.3% vs 86.3%, aHR 1.11, 95%CI 0.67-1.83). The results were similar among those who underwent nodal evaluation (5-year OS rates, 92.6%, 86.6%, and 89.4% for combination therapy, chemotherapy alone, and no adjuvant therapy), including grade 1 lesions (96.2%, 89.4%, and 100%, respectively). In grade 2 lesions, 5-year OR rates was modestly lower for no adjuvant therapy than combination therapy (89.4%, 84.0%, and 82.7% for combination, chemotherapy alone, and no adjuvant therapy, P = 0.03). For stage IIIA1 disease, omission of adjuvant therapy was associated with decreased OS compared to combination therapy (43.2% vs 73.1%, aHR 1.65, 95%CI 1.30-2.11) or chemotherapy alone (43.2% vs 67.1%, aHR 1.62, 95%CI 1.32-1.99). CONCLUSION: The results of this investigation suggest that survival effects of adjuvant therapy differ for stage IA3 and IIIA1 diseases. Patients with stage IA3 disease have overall good prognosis regardless of adjuvant therapy particularly grade 1 lesions, partly supporting the FIGO committee suggestion for adjuvant therapy de-escalation in stage IA3 endometrial cancer.

The significance of lower uterine segment involvement in endometrial cancer.

BACKGROUND: Limited data suggests lower uterine segment involvement (LUSI) in endometrial cancer may be associated with other poor prognostic factors. We assessed the unclear impact of LUSI on prognosis in endometrial cancer. METHOD: ology: A revision of pathological samples following surgical staging between the years 2002-2022 was performed and clinical data collected from patients' records. Characteristics and outcomes of women with and without LUSI were compared and analysed. Kaplan Meyer survival curves compared overall survival (OS) and progression-free survival (PFS). RESULTS: 429 women were included, of which 45 (10.5%) had LUSI. No differences were found between the groups regarding demographic or clinical characteristics. LUSI was significantly associated with lympho-vascular space invasion (40% vs. 22% p = 0.01), lymph node involvement (6.4% vs. 9.1%, p = 0.05), shorter PFS (4 vs. 5.5 years, p = 0.01) and OS (5.6 vs. 11.5 years, p = 0.03). Multivariate analysis showed higher hazard ratios for OS and PFS (1.55 95%CI 0.79-3.04 and 1.29 95%CI 0.66-2.53, respectively) but these were insignificant even in a sub-analysis of endometrioid histology (1.76 95%CI 0.89-3.46 and 1.35 95%CI 0.69-2.65, respectively). A trend towards decreased PFS and OS was demonstrated in the Kaplan Meyer survival curves for all cases (log rank test p = 0.5 and 0.29 respectively), endometrioid histology (log rank test p = 0.06 and 0.51 respectively) and early-stage disease (log rank test p = 0.63 and 0.3 respectively). CONCLUSION: LUSI may be related to poorer outcome of endometrial cancer and may represent an additional factor to consider when contemplating adjuvant treatment, especially in endometrioid-type and early-stage disease.

Assessment of endometrial carcinoma on biopsy as a predictor of final surgical pathology: Are we doing it right? A completed audit cycle and recommendations.

Background: Typing and grading of endometrial carcinomas (ECs) on small biopsy specimens is crucial to determine the need for full surgical staging. Histological subtype and grade are key factors available for risk stratification before surgery. However, this can be diagnostically challenging on small biopsy specimens, especially when morphologic features are subtle or overlapping. Aims: The aims of this audit were to assess concordance of endometrial carcinomas on biopsy specimens with hysterectomy specimens and to determine if the immunohistochemistry (IHC) panel being used in our practice was adequately subtyping ECs. Settings and Design: The audit was approved by the Clinical Effectiveness Team of the Royal College of Pathologists (UK) as meeting all the criteria and standards set out by the College. Materials and Methods: Biopsies from 67 cases of EC were compared for histological subtype and grade of endometrioid carcinoma with resection specimens. A re-audit was carried out on 59 cases after implementation of changes recommended by the initial audit. Results: Two of 35 (6%) tumours defined as G1 on biopsy were upgraded (to G2) on final pathology, as was one of 7 (14%) G2 tumours (to G3). One of these cases had solid areas just amounting to more than 6% on resection. In the second case, a comment was made that assessment had been difficult as the specimen was suboptimally fixed, but nuclei appeared atypical. Of seven G2 biopsies, one case was upgraded to grade 3 on final pathology based on proportion of solid areas. Our data show lower rates of discordance as compared to previous studies and on re-audit, the concordance between endometrioid and nonendometrioid serous carcinoma improved with the addition of immunohistochemistry (IHC) for Phosphatase and tensin homolog (PTEN) to biopsies. Conclusions: PTEN IHC can complement other stains and aid in the distinction of grade 3 endometrioid carcinoma from serous carcinoma on endometrial biopsies.

To study the expression of estrogen, progesterone receptor and p53 immunohistochemistry markers in subtyping endometrial carcinoma.

Background: Endometrial cancer is one of the most commonly diagnosed cancers in women worldwide. Aim and Objectives: To study the expression of estrogen receptor (ER), progesterone receptor (PR) and p53 immunohistochemistry (IHC) markers in subtyping endometrial carcinoma. Materials and Methods: A total of 100 cases of carcinoma endometrium submitted during January 2016 to October 2018 were included in our study. The ER, PR and p53 expressions were scored as per the adopted scoring system. Agreement between ER, PR and p53 IHC expression and the consensus HE diagnosis, FIGO grading and tumour staging were assessed using Chi square tests. Results: There was a statistical association between ER, PR and p53 status and tumour histologic type with a P value < 0.01. There was no statistical significance observed between ER and PR expressions and different FIGO grades. Statistical significance (P = 0.036) between p53 and different FIGO grades seen. No statistical significance was observed between ER, PR and p53 expressions and different tumour stages and tumour invasiveness. There was a statistical association between ER and PR status and lymph node metastasis. p53 did not show a statistical significance. Conclusion: Combination of ER, PR and p53 IHC markers can be used to distinguish type 1 and type 2 endometrial cancers. PR expression is more specific than ER in endometrioid carcinomas. p53 expression is more specific in serous carcinoma, however, p53 IHC alone cannot be used to distinguish different grades of endometrioid carcinomas as there is variability of staining in endometrioid carcinomas.

Integration of the Molecular Classification of Endometrial Carcinoma to Select Patients for Fertility Sparing Strategies.

Fertility-sparing treatment (FST) for endometrial carcinoma (EC) is an option for a subgroup of young women with low-risk disease. The low-risk group comprises patients with endometrioid EC stage IA, grade 1, with or without focal lymphovascular invasion. In the era of molecular subtyping, treatment de-escalation for some EC subtypes is recommended. Recommendations for fertility-preserving treatments were developed regardless of the molecular classification of EC. However, few studies have focused on this topic. In this review, we summarize the actual data available in the literature and discuss the impact of some molecular subtypes of FST.

Prognosis of polymerase epsilon (POLE) mutation in high-grade endometrioid endometrial cancer: Systematic review and meta-analysis.

BACKGROUND: POLE mutated endometrial carcinomas may represent a subspecific type of tumors harboring a more favorable prognosis. Grade 3 (G3 or high-grade) endometrioid endometrial carcinomas remain a clinical dilemma, with some tumors behaving as the low-grade counterparts and others presenting a more aggressive behavior. OBJECTIVES: To determine the association between POLE mutational status and the overall-survival (OS) and progression-free-survival (PFS) of patients with G3 endometrioid endometrial cancer (EC). We also aimed to determine the prevalence of POLE mutations in G3 endometrioid EC. METHODS: We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO No: CRD4202340008). We searched the following electronic databases: PubMed/Medline, EMBASE, Cochrane Library, Scopus, and Web of Science. For time-to-event data, the effect of POLE mutation in G3 EC was described using hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). Individual patient data for each study was investigated if available from the study authors. If individual patient data were not available, information regarding time-to-event outcomes was extracted using an appropriate methodology. OS and PFS were analyzed using both one-stage and two-stage approaches, the Kaplan-Meier method, and Cox-proportional hazards models. RESULTS: This systematic review and meta-analysis included 19 studies with 3092 patients who had high-grade endometrioid EC. Patients with POLE mutations had lower risks of death (HR = 0.36, 95% CI 0.26 to 0.50, I2 = 0%, 10 trials) and disease progression (HR = 0.31, 95% CI 0.17 to 0.57, I2 = 33%, 10 trials). The pooled prevalence of POLE mutation was 11% (95% CI 9 to 13, I2 = 68%, 18 studies). CONCLUSION: POLE mutations in high-grade endometrioid EC are associated with a more favorable prognosis with increased OS and PFS.

Endometrioid type adenocarcinoma in situ as a potential precursor lesion for extremely rare invasive endometrioid type adenocarcinoma of the cervix.

HPV-independent in situ adenocarcinomas have been only recently added to the WHO 2020 classification. To date, little information has been published about HPVindependent precursor lesions. In particular, regardiong the extremely rare cervical endometrioid type adenocarcinoma thought to arise in the setting of cervical endometriosis, a premalignant lesion is still not well defined. In this short communication we describe a possible precursor to invasive cervical endometrioid type adenocarcinoma in a 39-yr-old patient, with a previous history of breast cancer.

PAX2 is regulated by estrogen/progesterone through promoter methylation in endometrioid adenocarcinoma and has an important role in carcinogenesis via the AKT/mTOR signaling pathway.

Endometrioid adenocarcinoma (EEC) is one of the most common cancers of the female reproductive system. In recent years, much emphasis has been placed on early diagnosis and treatment. PAX2 (Paired box 2) inactivation is reportedly an important biomarker for endometrioid intraepithelial neoplasia (EIN) and EEC. However, the role of PAX2 in EEC carcinogenesis remains unclear. PAX2 expression and associated clinical characteristics were analyzed via The Cancer Genome Atlas, Gene Expression Omnibus, and Cancer Cell Line Encyclopedia databases and clinical paired EIN/EEC tissue samples. Bioinformatic analysis was conducted to identify the putative molecular function and mechanism of PAX2. Cell proliferation, colony formation, cell migration, and invasion assays in vitro, and mouse xenograft models were utilized to study the biological functions of PAX2 in vivo. Pyrosequencing and the demethylating drug 5-Aza-dc were used to verify promoter methylation in clinical tissues and cell lines, respectively. The mechanism underlying the regulatory effect of estrogen (E2) and progesterone (P4) on PAX2 expression was investigated by receptor block assay and double luciferase reporter assay. PAX2 expression was found to be significantly downregulated in EIN and EEC tissues, its overexpression inhibited EEC cell malignant behaviors in vivo and in vitro and inhibited the AKT/mTOR signaling pathway. PAX2 inactivation in EEC was related to promoter methylation, and its expression was regulated by E2 and P4 through their receptors via promoter methylation. Our findings elucidated the expression and function of PAX2 in EEC and have provided hitherto undocumented evidence of the underlying molecular mechanisms. PAX2 expression is suppressed by estrogen prompting its methylation through estrogen receptor. Furthermore, PAX2 regulates the AKT/mTOR signaling pathway to influence EEC progression. © 2024 The Pathological Society of Great Britain and Ireland.

Prediction of lymph node metastasis based on tumor size in stage 1A endometrioid endometrium cancer.

OBJECTIVE: Endometrium cancer (EC) is the most prevalent cancer affecting women in developed countries. There is debate about the need to perform lymphadenectomy in cases with a tumor diameter >2 cm. The aim of our study is to research the prediction of lymph node metastasis using tumor size in stage 1A endometrioid endometrium cancer (EEC). PATIENTS AND METHODS: The study enrolled cases operated in the clinic due to stage 1A EEC (FIGO 2009) from December 2010-2021. The correlations of age, age interval, parity, type of operation, tumor diameter, myometrial invasion, histological grade, and lymph node metastasis were statistically analyzed. The cut-off point for tumor size was determined with the ROC curve and Youden index. RESULTS: The study analyzed a total of 292 cases, and the mean age of cases was 62.3±10.0 years. Of the cases, 79.5% had histological grade 1, and 20.5% had grade 2. Myometrial invasion ≤50% was detected in 69.5%, and no myometrial invasion was detected in 30.5%. The mean tumor diameter was 34.0±18.0. Lymph node metastasis was identified in 6 cases (2.1%). Based on the tumor diameter cut-off value of 35 mm, sensitivity was 100%, and specificity was 50.3%. 116 cases with tumor diameter >35 mm and 176 with diameter ≤35 mm, and grade 2 histology and lymph node positivity were found statistically significant between these groups (respectively, p=0.012 and p=0.038). The lymph node metastasis risk was 0% in cases with tumor diameter ≤35 mm, while it was 5.2% in cases with tumor diameter >35 mm. CONCLUSIONS: The general approach in stage 1A EEC is not to perform lymphadenectomy. However, when the tumor diameter is noted, lymphadenectomy may be considered as the lymph node metastasis risk increases in cases with a tumor diameter of 35 mm or more. There is a need for more clinical studies on this topic.