Cases Of Endometrial Carcinoma Research Articles

The spectrum of oestrogen receptor expression in endometrial carcinomas of no specific molecular profile.

Decreased oestrogen receptor (ER) expression is a marker of poor prognosis in endometrial carcinomas (EC) of no specific molecular profile (NSMP), but the optimal cut-off to separate high-risk 'low ER' versus low-risk 'high ER' expression has not been defined. Here we characterised the distribution of ER staining in a cohort of ECs. Biopsy specimens from 120 cases of NSMP EC were stained for ER and assigned an Allred score. In 66 additional cases ER staining of matched biopsy and hysterectomy were compared. Twelve of 120 tumours had an Allred score of 0-3, including three endometrioid carcinomas (EEA) (one G1, two G3), four clear cell carcinomas (CCC), two mesonephric-like adenocarcinoma (MLA) and one each of: gastric-type adenocarcinoma, carcinosarcoma and endometrial carcinoma NOS. Three had Allred scores of 4-5: two MLA and one high-grade carcinoma with yolk sac differentiation. Five had Allred scores of 6: four EEA (one G1, one G2, two G3) and one mixed clear cell and endometrioid carcinoma. The remaining 100 tumours with Allred scores ≥ 7 were all EEA (66 G1, 28 G2, five G3 and one grade unknown). Comparing the biopsy versus hysterectomy ER staining (n = 66), the results were within a single Allred score point, except two cases with strong diffuse expression in the biopsy (Allred 8) and moderate expression in the hysterectomy (Allred 5). Most NSMP ECs (> 80%) show high ER expression (Allred score ≥ 7). All non-endometrioid carcinomas and a few endometrioid carcinomas had lower ER expression (Allred score ≤ 6) or were completely negative.

Correlation between immunohistochemical staining and clinicopathological findings in endometrial carcinoma.

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. 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. 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. These findings highlight the importance of MMR and p53 immunohistochemical staining in the classification, and prognosis of endometrial carcinoma.

Impact of hormonal contraception on endometrial histology in patients with Lynch syndrome, a retrospective pilot study.

Hormonal contraception (HC) is a well-recognized protection against endometrial cancer (EC) in the general population. It has not been established if this is also applicable to women with Lynch syndrome (LS), a condition associated with a up to 50% lifetime risk of developing EC. The objective of this study was to evaluate if the use of HC influences the incidence of endometrial hyperplasia and EC in women with LS by comparing the histology of annual endometrial biopsies obtained in patients with LS who are using HC versus non-users. This is a retrospective cohort study conducted with endometrial biopsies obtained in women 30 to 50 years of age with LS. The Pearson Chi-square test was performed to compare the prevalence of cancer and hyperplasia in the HC users and in the non-HC users groups. A total of 164 endometrial biopsies obtained among 75 women were suitable for analysis. Among the 86 biopsies obtained in the non-HC group, 81.4% (70/86) were normal. Two cases of endometrial carcinoma (2.3%) and 6 endometrial hyperplasia without atypia were found (7.0%). Among the 78 biopsies performed in patients using HC, 78.2% (61/78) were normal. Three endometrial hyperplasia without atypia (3.8%) and three cases of EC were diagnosed (3.8%). This study suggests that, in women of 30 to 50 years of age with LS, the use of hormonal contraception does not seem to decrease the occurrence of endometrial hyperplasia/carcinoma on annual endometrial histology.

The volumetric ADC histogram analysis in differentiating stage IA endometrial carcinoma from endometrial polyp.

This study aimed to explore the value of apparent diffusion coefficient (ADC) histogram based on whole lesion volume in distinguishing stage IA endometrial carcinoma from the endometrial polyp. MRI of 108 patients with endometrial lesions confirmed by pathology were retrospectively analysed, including 65 cases of stage IA endometrial carcinoma and 43 cases of endometrial polyp. The volumetric ADC histogram metrics and general imaging features were evaluated and measured simultaneously. All the features were compared between the 2 groups. The receiver operating characteristic curve was utilized to evaluate the diagnostic performance. The mean, max, min, and percentiles (10th, 25th, 50th, 75th, 95th) ADC values of endometrial carcinoma were significantly lower than that of polyp (all P < .05). The skewness and kurtosis of ADC values in the endometrial carcinoma group were significantly higher than those in the endometrial polyp group, and the variance of ADC values in the endometrial carcinoma group was lower than those in the endometrial polyp group (all P < .05). Endometrial carcinoma demonstrated more obvious myometrial invasion combined with intralesion haemorrhage than polyp (all P < .05). The 25th percentile of ADC values achieved the largest areas under the curve (0.861) among all the ADC histogram metrics and general imaging features, and the sensitivity and specificity were 83.08% and 76.74%, with the cut-off value of 1.01 × 10-3 mm2/s. The volumetric ADC histogram analysis was an effective method in differentiating endometrial carcinoma from an endometrial polyp. The 25th percentile of ADC values has satisfactory performance for detecting malignancy in the endometrium. The ADC histogram metric based on whole lesion is a promising imaging-maker in differentiating endometrial benign and malignant lesions.

Caveolin-1‘s dual impact on endometrioid endometrial carcinoma: a histopathological and immunohistochemical study

ABSTRACT The objectives of this study are to evaluate caveolin-1 expression in endometrioid endometrial cancer and its correlation with clinicopathological parameters. Forty-four cases of endometrioid endometrial carcinomas underwent radical hysterectomy. The archived paraffin sections that were stained for caveolin-1 by immunohistochemistry, caveolin-1 expression were detected in cancerous epithelial cells in 18.2% of the cases, and stromal caveolin-1 was detected in 65.9% of the cases. Caveolin-1 expression in the epithelium showed a significant positive association with the T stage and the FIGO stage. Positive caveolin-1 expression in epithelium has a direct, positive and significant relationship with invasion of other organs and a direct and significant relationship with the advanced FIGO stage. As for caveolin-1 expression in the stroma, it showed a significant negative inversely significant association with myometrial invasion. Also, there is a significant negative association between caveolin-1 expression in the epithelium and its expression in the stroma. We conclude that caveolin-1 expression strongly plays a critical role in endometrioid endometrial carcinoma as a tumor suppressor or promoter of invasion. In early lesions, high stromal levels appear to be protective against progression. While decreased stromal expression and increased epithelial expression were associated with aggressive tumors.

Clinicopathological Significance of Nucleosome Remodeling and Deacetylase Complex Expression in Endometrial Carcinoma.

Only a few studies have examined the expression of nucleosome remodeling and deacetylase complex in endometrial carcinoma (EC). The aim of this study was to analyze the expressions of histone deacetylase (HDAC1), HDAC2, and chromodomain helicase DNA-binding protein 4 (CHD4) in EC. Sixty cases of EC were categorized into two clusters based on the expression levels of the three proteins. Cluster 1 (C1) exhibited elevated expressions of HDAC2 and CHD4 compared with cluster 2 (C2). Notably, 75% of cases in C2 represented non-aggressive histological types, whereas 37.5% of cases in C1 manifested aggressive types. C2 exclusively comprised pathological tumor stage 1 (pT1) tumors, whereas C1 included pT2 and pT3 tumors. In C1, 25% of cases displayed aberrant p53 expression, contrasting with the absence of such expression in C2. Furthermore, only one patient in C2 experienced disease recurrence, whereas 20.8% of patients in C1 developed recurrent tumors. High HDAC2 and CHD4 expression may be associated with adverse clinicopathological characteristics in EC. Further studies are needed to validate these results.

Diagnostic, prognostic, and predictive importance of neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and CA125 in endometrial hyperplasia and carcinoma.

Inflammation has an important role in the progression of endometrial carcinoma. The aim of this study is to find the association between neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and CA125 in endometrial hyperplasia and endometrial carcinoma. The study also focuses on the association of CA125, NLR, and PLR with histopathological parameters in endometrial carcinoma that are of prognostic importance. This is a prospective cross-sectional study on 57 biopsy-proven cases of endometrial hyperplasia and carcinoma conducted over a period of two years. The NLR, PLR, and CA125 were calculated and recorded in all the 57 cases. The 57 cases were divided into three groups: endometrial hyperplasia without atypia group which included 36 cases, endometrial atypical hyperplasia group which included 10 cases, and the endometrial carcinoma group which included 11 cases. Comparison was done between the groups, and parity, NLR, PLR, and CA125 were found to be significant, but patient age and postmenopausal status were not significant. NLR, PLR, and CA125 were found to increase with higher grade, pT-stage, and nodal stage for the endometrial carcinoma cases. NLR, PLR, and CA125 were marginally increased or normal in the case of endometrial hyperplasia without atypia and endometrial atypical hyperplasia, while they were significantly increased in endometrial carcinoma, and also correlated with an increase in grade, pT-stage, and nodal stage. Hence, these can be considered for additional screening as diagnostic, prognostic, and predictive markers in case of abnormal uterine bleeding with endometrial pathology.

Abstract IA012: The role of the serine/threonine phosphatase PP2A in endometrial cancer development and progression: lessons learned from mutations and small molecules

Abstract Uterine cancer is the most common gynecologic malignancy in the United States with approximately 60,000 new diagnoses each year. While many cases of uterine endometrial carcinoma (EMCA) have favorable outcomes with recurrence-free long-term survival, outcomes for the high-grade, treatment-refractory histological subtypes, including uterine serous carcinoma (USC) and uterine carcinosarcoma (UCS), remain an important clinical problem. Uterine serous carcinomas and uterine carcinosarcomas tumors are the most aggressive subtypes of uterine cancer, displaying a high propensity to invade the peritoneal cavity and to metastasize to distant sites. Accordingly, 50-70% of high-grade tumors exhibit extrauterine spread at time of initial surgery and have limited treatment options. The inherent aggressiveness of these tumors suggests that they are intrinsically equipped to disseminate and propagate tumors at secondary sites. The molecular drivers of this phenotype, however, have yet to be completely characterized. A lack of established and validated molecular drivers of the high-grade subtypes, especially those that are responsible for the high rate of metastasis, has limited the use of targeted treatment strategies. However, we and other groups have shown that PPP2R1A, the scaffolding subunit of the tumor suppressor protein phosphatase 2A, is mutated in up to 40% of USC patients, and these recurrent mutations are found at both the primary and metastatic sites. These mutations are heterozygous, and two specific mutations: P179R and S256F, occur exclusively within these high-grade subtypes of uterine cancer (i.e., are not found in any other cancer type). PP2A, is a family of serine/threonine phosphatases, where the active heterotrimeric form of the enzyme is comprised of a catalytic (C) subunit, a scaffolding (A) subunit, and a substrate directing regulatory (B) subunit. In aggregate, PP2A is considered a tumor suppressor protein, but certain heterotrimers have tumor promoting roles. Here we present data related to the molecular and biological basis through which these recurrent pathogenic mutations drive endometrial cancer development and progression using disease relevant cellular and in vivo model systems. Additionally, building from previously published work from our group, we have developed a novel series of small molecule molecular glues (PMGs) that specifically correct the mutant heterotrimer driving tumor regressions in both cellular and patient derived xenograft models of high-grade endometrial cancer. Collectively, this data suggests that recurrent pathogenic mutations in the PPP2R1A gene drive endometrial cancer pathogenesis and these mutations can be therapeutically targeted using a series of pharmaceutically tractable small molecules. Citation Format: Goutham Narla. The role of the serine/threonine phosphatase PP2A in endometrial cancer development and progression: lessons learned from mutations and small molecules [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr IA012.

Analysis of Characteristics of Endometrial Carcinoma in Peri- and Postmenopausal Women with Abnormal Uterine Bleeding.

To analyze the menstrual characteristics of endometrial carcinoma and investigate whether abnormal uterine bleeding in the perimenopausal period differs from postmenopausal bleeding. We conducted a retrospective analysis of 928 cases of endometrial carcinoma in patients admitted from January 2016 to December 2022. We gathered fundamental clinical data and analyzed distinct clinical risk factors between the perimenopausal and postmenopausal groups. Furthermore, we computed the statistical variances in menarche, regular menstrual cycles, and the duration of abnormal uterine bleeding. Perimenopausal patients with endometrial carcinoma exhibit similar factors to postmenopausal patients, especially if they have a history of menstrual cycles lasting more than 30 years, hypertension, abnormal uterine bleeding for over 1 year, and a high risk of endometrial carcinoma. Early intervention for abnormal uterine bleeding during the perimenopausal stage can prevent up to 80% of women from developing endometrial carcinoma. Perimenopause women experiencing abnormal uterine bleeding should be mindful of the risk of endometrial carcinoma, as this awareness can substantially decrease the occurrence of the disease.

Immunohistochemical Study of Estrogen and Progesterone Receptor Expression in Endometrial Carcinoma

BACKGROUND: Endometrial cancer is the fourth most common cancer affecting the women both from the point of view of incidence as well as mortality. ER/PR positivity helps to determine the need for hormonal treatment for endometrial cancer. METERIAL AND METHOD It is a reterospective study on 22 histopathologically proven cases of endometrial carcinoma between the age group 30 to 80 yr from 1 Jan 2021 to 30 June 2022. Those cases with inadequate sample or with history of pregnancy were excluded from study. ER and PR expression was seen with Immunohistochemistry kit protocol. RESULTS: Mean age of patients was 57.77 yrs. Endometrial carcinoma is more common in postmenopausal females. Bleeding per vaginum is the chief complaint. Most of the cases were well differentiated and of low grade.ER expression is positive in (15/17 88.2% )of cases of low grade /well differentiated , (4/4,100%) in moderately differentiated and not seen in high grade/ poorly differentiated endometrial carcinoma .PR expression seen in low grade/well differentiated is (14/17,82.4%) , in moderately differentiated is( 4/4,100%) and in high grade /poorly differentiated is (1/1, 100%)and not seen in high grade or poorly differentiated endometrial carcinoma .As the tumor invades deep in the myometrium ER and PR expression decreases. CONCLUSION: ER and PR are important prognostic biomarkers to predict response to anti hormonal therapy.

Prognostic factors of patients with recurrent uterine malignancies undergoing secondary cytoreductive surgery.

Several studies have demonstrated that secondary cytoreductive surgery (SCS) for patients with recurrent uterine malignancies may improve the survival. However, the selection criteria for SCS remain to be defined. This study aimed to assess the outcome of SCS and to explore factors that may influence the prognosis. Data of patients with recurrent uterine malignancies who received SCS in our hospital between January 2005 and January 2015 were retrospectively analyzed. Patients were assigned into endometrial carcinoma (EC) group and uterine sarcoma (US) group. 84 cases in total were involved in the study, including 47 cases with recurrent EC and 37 cases with recurrent US. The 5-year survival of cases with recurrent EC and recurrent US was 59.6% and 33.3%, respectively. Recurrent EC cases with a lower tumor grade (G1/G1-G2/G2), size of the largest tumor ≤ 6cm, single recurrent tumor, a history of adjuvant therapy, as well as recurrent US cases with younger age, a longer disease-free interval (DFI) before SCS (≥ 12 months), no peritoneal dissemination, and a history of complete cytoreduction were associated with a longer survival. The number of recurrent tumors was found as an independent prognostic factor of SCS. Recurrent EC cases with a lower tumor grade, smaller tumor size, single tumor, a history of adjuvant therapy, as well as recurrent US cases with younger age, a longer DFI before SCS, no peritoneal dissemination, and a history of complete cytoreduction were more likely to benefit from SCS.

Diagnostic value of endometrial samples in women with abnormal uterine bleeding at a teritiary care centre

Abnormal uterine bleeding (AUB) is a most common gynecological complaint associated with co morbidities that affects quality of life in women. The Aim of the study was to ananlyze the hisopathological patterns of endometrium in women with AUB and to determine the various histopatterns among different age groups of women presenting with AUB. This is a prospective study conducted at Government medical college, Anantapuramu, from January 2021 to December 2022.Endometrial samples with clinical diagnosis of AUB, in whom Gestational causes were ruled out, were included in this study, Statistical data ananlysis was done using SSPS software. A total of 360 cases were analyzed. The prevalence of AUB most common in perimenopausal age group women. Mennorhagia (79.8%) was the common bleeding pattern. The bleeding pattern was significantly associated with age groups(p=0.00).The functional cause (64.2%) of AUB was more common than Organic cause (35.8%).The association of functional and organic causes with age group was not significant. The most common histological pattern was the normal cyclical pattern showing proliferative phase (54.1%). 94 cases showed hisopathological pattern of Hyperplasias that are more common among perimenopausal and postmenopausal age groups. Five cases of Endometrial carcinoma were seen among postmenopausal age group. Three cases were Stage IA, two cases were Stage IB. Obesity and hypertension were most common comorbid conditions seen in this study. Endometrial biopsy should be considered during the workup of women with a clinical diagnosis of AUB to exclude organic pathology especially early detection of precursor lesion of malignancy among perimenopausal and post-menopausal age groups.

Histopathological Analysis of Hysterectomy Specimens in a Tertiary Care Centre: A Retrospective Study.

Introduction The uterus is a crucial reproductive organ that is susceptible to the development of several non-neoplastic and neoplastic diseases in women, greatly increasing morbidity and mortality. Although there are various therapeutic options, hysterectomy is still a popular treatment option throughout the world.Abnormal uterine bleeding, pelvic pain, pelvic inflammatory disease (PID), prolapse of the uterus, adenomyosis, endometriosis, fibroids, gynecological malignancies, and obstetric problems that require hysterectomy, all samples must be examined histopathologically.Histopathological examination of the specimens obtained after hysterectomy is important for both diagnosis and treatment. The current work aimed to identify the various clinical indications, analyze the clinicopathological correlation in hysterectomy specimens, and analyze the patterns of lesions in hysterectomy specimens. Materials and methods This study was conducted in the Department of Pathology at the Datta Meghe Medical College, Wanadongari, Nagpur, from February 2022 to January 2023. All types of hysterectomy specimens received during this year were examined, and the tissues were processed and stained with H&E. Histopathological examination was performed, and various lesions in the hysterectomy specimens were examined.The study included all forms of hysterectomy, including abdominal, vaginal, laparoscopic, and total abdominal hysterectomy. Results An analysis of 110 cases of hysterectomy revealed that abdominal hysterectomy was the type of hysterectomy in 79 (71.82%) cases, with a maximum age range of 35 to 45 years (42.72%). The proliferative phase endometrium was the most common endometrial pathology, accounting for 43 (39.09%) cases, followed by the atrophic endometrium in 35 (31.82%) cases. Leiomyoma was the most prevalent myometrial lesion, accounting for 52 (47.28%) cases, followed by adenomyosis, accounting for 23 (20.91%) cases. Chronic cervicitis was the most common incidental finding in the hysterectomy samples, accounting for 85 (77.28%) cases. Follicular cysts, representing 22 (20%) cases, were the most common ovarian lesions, followed by serous cystadenoma in seven (6.37%) cases. Two cases of malignant tumors were noted: one case of endometrial carcinoma and one case of mucinous cystadenocarcinoma of the ovary. In most cases, ranging from 70% to 100%, the final histopathological diagnosis supports the preoperative clinical diagnosis. Conclusion Hysterectomy is the most common major gynecological surgery performed under elective conditions. Although histological studies and clinical diagnoses are closely correlated, several lesions, including chronic cervicitis and adenomyosis, were discovered incidentally. Therefore, every hysterectomy specimen must undergo a thorough histological investigation, even if it appears superficially normal, to confirm the diagnosis and improve postoperative care.

A rare case of poorly-differentiated endometrial carcinoma in a female-to-male transgender man on testosterone therapy

Abstract Introduction/Objective Testosterone is commonly used as gender-affirming therapy for transmasculine individuals. The effects of testosterone therapy on endometrial tissue are complex, with some experiencing atrophy, and others with abnormal uterine bleeding (AUB). Endometrial carcinomas in transgender men are rarely reported in the literature. Here we present a case of poorly-differentiated endometrial carcinoma in a transgender man on testosterone. Methods/Case Report A 56 year-old female-to-male transgender man who had been on testosterone and finasteride therapy since 2015 developed vaginal discharge in 2022. No history of abnormal pap smears was noted. The patient’s pelvic ultrasound that was subsequently obtained after presenting with the vaginal discharge showed a thickened endometrium of 4 cm thickness. PET-CT revealed hypermetabolic activity corresponding to the endometrial lining of the uterus. Endometrial biopsy was notable for poorly differentiated carcinoma with retained expression of the mismatch repair proteins by immunohistochemical stains. The patient underwent hysterectomy with bilateral salpingo-oophorectomy. Grossly, there was a 9.5 cm necrotic mass occupying the entire endometrial cavity, extending &amp;gt;50% into myometrium thickness and extending into the lower uterine segment, without cervical involvement. Background endometrium was inactive/atrophic. Microscopic examination of the tumor showed sheets of epithelioid tumor cells with extensive necrosis, without any glandular pattern. On immunohistochemical stains, the tumor cells were positive for pankeratin and patchy staining for keratin 7 and keratin 20, without expression of PAX8, estrogen receptor, progesterone receptor or androgen receptor. Results (if a Case Study enter NA) N/A Conclusion Gender-affirming testosterone is a common long-term treatment for transgender men. There is limited understanding of the long-term effects of testosterone therapy on endometrial pathology, particularly regarding the potential for developing malignancy. Positive staining for androgen receptor has been previously reported in endometrial malignancies, and therefore, studies on the potential effects of testosterone therapy on endometrial malignancies is warranted. This case demonstrates the importance of continued gynecologic care in female-to-male transgender individuals who have not undergone previous gender affirming gynecologic surgery.

Endometrial Carcinoma: A Comprehensive Analysis of Clinical Parameters, Treatment Modalities, and Prognostic Outcomes at a Tertiary Oncology Center in the UAE.

Background Endometrial carcinoma (EC) remains a pressing global health issue, with a discernible upsurge in incidence, especially in developed countries. Notably, the United Arab Emirates (UAE) has witnessed a surge in EC cases, demanding an in-depth, region-specific exploration into the disease's clinical, treatment, and prognostic facets against the backdrop of its unique socio-genetic and environmental contours. Aim This study aimed to profess a comprehensive understanding of EC by examining clinical parameters, treatment modalities, and prognostic outcomes in the UAE context, thereby seeking to delineate potential correlations between varied therapeutic combinations, patient demographics, and tumor characteristics in affecting prognostic outcomes. Materials and methods A retrospective cohort study involving 93 patients diagnosed with EC from January 2011 to March 2023 at a leading oncology center in the UAE was conducted. Data, including demographic information, clinical presentation, treatment modalities, and prognostic outcomes, were meticulously extracted and analyzed. The R software (version 4.2.2) facilitated exhaustive statistical analyses, involving descriptive statistics, correlation analyses with the polycor package, and survival analyses utilizing the Kaplan-Meier method and Cox regression analysis via the survival and survminer packages, respectively. Results Although the correlation matrix revealed a noticeable relationship between "Family history"and "Age," most parameters displayed independence, offering a robust platform for ensuing multivariate analyses. Kaplan-Meier survival curves, stratified by therapeutic modalities, exhibited no statistically significant survival differences across therapeutic cohorts (p-values: 0.44, 0.86, and 0.83). Conversely, the composite Cox regression model underscored "non-national" demographic, Diabetes Mellitus II, and stromal invasion as pivotal prognostic factors, indicating the multifactorial nature of survival in EC patients and emphasizing demographic and tumor characteristics over therapeutic modalities as influential prognostic determinants. Conclusion In conclusion, while therapy types were not directly correlated with survival, demographic and tumor traits prominently impacted prognostic outcomes, advocating for an intricate, multidimensional approach to managing EC in the UAE. This study hopes to sow seeds for subsequent research, shaping clinically and culturally apt practices and policies in the region's healthcare landscape.

The Evaluation of Endometrial Sampler SAP-1 in Screening Patients With General Risk of Endometrial Cancer: A Diagnostic Test Study

Objectives: In recent years, early screening for endometrial cancer (EC) has received increasing attention. EC screening is recommended to be conducted among high-risk and risk-increasing populations, while the general-risk population, even with symptoms, is not within the scope of screening. This study aims to explore the role of endometrial sampler SAP-1 as a sample-collecting tool to screen EC among patients with general risk. Materials and Methods: From August 2018 to June 2023, 275 patients, who were hospitalized for undergoing hysteroscopy and were confirmed as having a general risk of EC, were enrolled in this retrospective study. Before the procedure, endometrial samples were firstly collected by the method of SAP-1, and then hysteroscopy curettage or electrotomy was conducted to gather endometrial samples. With the pathological results of the latter as the gold standard, the diagnostic efficacy of SAP-1 sampling was analyzed. Results: The sample satisfaction rate of SAP-1 was 91.4%, slightly lower than that by method of hysteroscopy (95.1%), but there was no significant difference between the two methods (P&gt;0.05). The samples of 275 cases were satisfied with both methods. One case of endometrial carcinoma and one case of precancerous lesion were misdiagnosed as normal endometrium with SAP-1 sampling. The sensitivity, specificity and accuracy of SAP-1 in diagnosing endometrial carcinoma and precancerous lesions were 88.2%, 100% and 99.3%, respectively. Conclusions: Applying endometrial sampler SAP-1 to screen EC among women with general risk of EC has high diagnostic efficiency, easy manipulation, high safety, and can be completed in outpatient service with outstanding cost-effectiveness, which as well is worthy of clinical promotion.

USP14 predicts poorer survival outcomes and promotes tumor progression in endometrial carcinoma by activating NF-κB signaling.

Ubiquitin-specific protease 14 (USP14), a member of the USP family, which catalyzes ubiquitin cleavage from a range of protein substrates, has been found dysregulated in several cancers. Our aim is to explore the functions and mechanism of USP14 in endometrial carcinoma (EC). Quantitative real-time PCR (qRT-PCR) and western blot (WB) were used to assess USP14 levels in EC tissues and adjacent nontumor tissues. USP14 overexpression or knockdown models were adopted to determine USP14-mediated effects on EC cell proliferation, migration, invasion, apoptosis, and epithelial-mesenchymal transition (EMT). The xenograft tumor experiment checked the effect of USP14 overexpression on tumor cell growth. Furthermore, the upstream signaling pathway of USP14 was predicted by bioinformatics. Consequently, EC tissues exhibited USP14 overexpression compared to normal paracancerous nontumor tissues. USP14 presence was linked to an adverse prognosis in EC cases. Functionally, USP14 overexpression reduced apoptosis and increased cell migration, invasion, and EMT in vivo and ex vivo. USP14 knockdown had the opposite effect. Mechanistically, NF-κB pathway activation occurred through the inhibitory effect of USP14 on I-κB expression. Conversely, NF-κB pathway inhibition attenuated USP14-mediated carcinogenic effects. Additionally, there existed a binding interaction between miR-124-3p and the 3'-UTR of USP14, resulting in USP14 activity inhibition. In summary, our research indicates that the involvement of miR-124-3p in USP14 regulation contributes to exacerbated EC progression through NF-κB pathway activation. The modulation of this pathway may be a new strategy for treating EC.

Comprehensive assessment of mismatch repair and microsatellite instability status in molecular classification of endometrial carcinoma

Objective: To explore the concordance and causes of different mismatch repair (MMR) and microsatellite instability (MSI) detection results in endometrial carcinoma (EC) molecular typing. Methods: A total of 214 EC patients diagnosed from January 2021 to April 2023 were selected at the Department of Pathology, Peking University Third Hospital. The immunohistochemistry (IHC) results of MMR protein were reviewed. Tumor specific somatic mutations, MMR germline mutations, microsatellite scores and tumor mutation burden (TMB) were detected by next-generation sequencing (NGS) with multi-gene panel. Methylation-specific PCR was used to detect the methylation status of MLH1 gene promoter in cases with deficient MLH1 protein expression. In cases with discrepant results between MMR-IHC and MSI-NGS, the MSI status was detected again by PCR (MSI-PCR), and the molecular typing was determined by combining the results of TMB and MLH1 gene promoter methylation. Results: (1) In this study, there were 22 cases of POLE gene mutation subtype, 55 cases of mismatch repair deficient (MMR-d) subtype, 29 cases of p53 abnormal subtype, and 108 cases of no specific molecular profile (NSMP). The median age at diagnosis of MMR-d subtype (54 years old) and the proportion of aggressive histological types (40.0%, 22/55) were higher than those of NSMP subtype [50 years old and 12.0% (13/108) respectively; all P<0.05]. (2) Among 214 patients, MMR-IHC test showed that 153 patients were mismatch repair proficient (MMR-p), 49 patients were MMR-d, and 12 patients were difficult to evaluate directly. MSI-NGS showed that 164 patients were microsatellite stable (MSS; equal to MMR-p), 48 patients were high microsatellite instability (MSI-H; equal to MMR-d), and 2 patients had no MSI-NGS results because the effective sequencing depth did not meet the quality control. The overall concordance between MMR-IHC and MSI-NGS was 94.3% (200/212). All the 12 discrepant cases were MMR-d or subclonal loss of MMR protein by IHC, but MSS by NGS. Among them, 10 cases were loss or subclonal loss of MLH1 and (or) PMS2 protein. Three discrepant cases were classified as POLE gene mutation subtype. In the remaining 9 cases, 5 cases and 3 cases were confirmed as MSI-H and low microsatellite instability (MSI-L) respectively by MSI-PCR, 6 cases were detected as MLH1 gene promoter methylation and 7 cases demonstrated high TMB (>10 mutations/Mb). These 9 cases were classified as MMR-d EC. (3) Lynch syndrome was diagnosed in 27.3% (15/55) of all 55 MMR-d EC cases, and the TMB of EC with MSH2 and (or) MSH6 protein loss or associated with Lynch syndrome [(71.0±26.2) and (71.5±20.1) mutations/Mb respectively] were significantly higher than those of EC with MLH1 and (or) PMS2 loss or sporadic MMR-d EC [(38.2±19.1) and (41.9±24.3) mutations/Mb respectively, all P<0.01]. The top 10 most frequently mutated genes in MMR-d EC were PTEN (85.5%, 47/55), ARID1A (80.0%, 44/55), PIK3CA (69.1%, 38/55), KMT2B (60.0%, 33/55), CTCF (45.5%, 25/55), RNF43 (40.0%, 22/55), KRAS (36.4%, 20/55), CREBBP (34.5%, 19/55), LRP1B (32.7%, 18/55) and BRCA2 (32.7%, 18/55). Concurrent PTEN, ARID1A and PIK3CA gene mutations were found in 50.9% (28/55) of MMR-d EC patients. Conclusions: The concordance of MMR-IHC and MSI-NGS in EC is relatively high.The discordance in a few MMR-d EC are mostly found in cases with MLH1 and (or) PMS2 protein loss or MMR protein subclonal staining caused by MLH1 gene promoter hypermethylation. In order to provide accurate molecular typing for EC patients, MLH1 gene methylation, MSI-PCR, MMR gene germline mutation and TMB should be combined to comprehensively evaluate MMR and MSI status.

Laparoscopic Sentinel Lymph Node Mapping Using NIR Fluorescence with ICG in Early Endometrial Cancer: Experience at a Tertiary Care Oncology Centre

Objective: To determine the detection rates and location of sentinel nodes as well as to determine intraoperative and postoperative surgico-pathological outcomes in endometrial cancer patients who underwent laparoscopic staging with sentinel node biopsy using ICG dye. Materials and Methods: This retrospective study was conducted in a tertiary care oncology centre, Amrita Institute of medical sciences, Kochi from April 2021 to March 2023. All cases of biopsy proven early stage endometrial carcinoma that underwent laparoscopic staging with SLN mapping using the ICG dye were included. All histological types were included, as long as the disease was confined to the uterus, clinically and on MRI. Results: A total of 80 patients were found eligible for the study. Only the patients with apparent uterine confined disease on preoperative MRI were selected for sentinel mapping, 80 % of whom had IA disease on MRI, and 20 % had IB, 13.5 % were high grade histology.The overall SLN detection rate was 93.75%, and bilateral detection rate was 92.5 %. Most common location was external iliac in 40.8% cases. Only 1 patient was found to harbour nodal micro metastasis on ultrastaging. Final histopathology identified stage IA in 63 (78.75%) patients, IB in 14 (17.5%), Stage II in 2 (2.5%) and Stage IIIC1 in 1 (1.25%) patient. Conclusion: Laparoscopic staging with SLNB using ICG is a practicable approach for uterine limited disease on preoperative evaluation. It extends the benefits of minimally invasive surgery to these patients, while overcoming the limitations of prohibitive cost or availability of expensive robotic equipment.

SAT211 PTH-secreting Endometrial Carcinoma: A Rare Cause of Hypercalcemia

Abstract Disclosure: E. Fanous: None. P. Park: None. L. Rakhlin: None. Introduction: Hypercalcemia of malignancy (HCM) is a common occurrence in advanced cancer, but it is rare for gynecological malignancies to be the cause (1). Case Presentation: Our patient is a 48-year-old postmenopausal female with diabetes mellitus and obesity who presented with pelvic pain and vaginal spotting over the course of 2 months. She also reported unintentionally losing approximately 60 lbs over the past year. A CT scan of the pelvis revealed a 6.1 cm uterine mass and thickening of the endometrium up to 2.4 cm. Her electrolyte levels were normal at the time of presentation. A biopsy of the endometrium was performed, and the pathology report indicated endometrial carcinoma. The patient was scheduled for a total hysterectomy and bilateral salpingo-oophorectomy (TAH/BSO). A few weeks prior to her scheduled surgery, the patient reported increased thirst and urination, which she attributed to her diabetes and intake of an SGLT2 inhibitor. On the day of surgery, she was found to have a calcium level of 15.4 mg/dl and an albumin level of 3.6 g/dl. She denied taking calcium supplements or Vitamin D3. The workup for hypercalcemia revealed a PTH level of 338 pg/ml, an undetectable PTH-rp level, and normal levels of Vitamin D1,25 and Vitamin D25. Additional imaging showed numerous pulmonary nodules, which were later confirmed to be metastases from endometrial carcinoma. The thyroid gland and surrounding soft tissue were noted to be unremarkable on available CT images. The patient received a single dose of zolendronic acid and was started on cinacalcet 30 mg twice a day. The calcium gradually normalized. She was initiated on chemotherapy with paclitaxel and carboplatin and underwent a palliative TAH/BSO. Cinacalcet was discontinued after several cycles of chemotherapy. Two months later, the PTH level was checked and found to be 34 pg/ml, with a normal calcium level of 9.5 mg/dl and an albumin level of 4.1 g/dl. Given that the hypercalcemia resolved and the PTH level normalized after chemotherapy and hysterectomy, it is believed that the endometrial carcinoma was the source of ectopic PTH. Conclusion: Approximately 5% of gynecological malignancies are associated with paraneoplastic hypercalcemia [1]. We present a rare case of PTH-secreting endometrial carcinoma, in which surgery and chemotherapy resulted in complete resolution of hypercalcemia and normalization of PTH. Clinicians should consider ectopic PTH production as part of the differential diagnosis in patients who present with malignancy and hypercalcemia.