Cases Of Endometrial Carcinoma Research Articles

Histopathological spectrum of uterine lesions in hysterectomy specimens of patients with abnormal uterine bleeding

Background: Abnormal uterine bleeding (AUB) is an overarching term that reflects any departure from normal menstruation or regular menstrual cycle patterns. Treatment depends upon the cause. Hysterectomy being a definite treatment for structural uterine pathology. Methods: This cross-sectional observational study was conducted in department of pathology, Netaji Subhash Chandra Bose medical college Jabalpur (M.P.). The study comprised of 140 hysterectomy specimens with or without salpingo-oophorectomy obtained from AUB patients and submitted for histopathological examination in our department during study period of 18 months. The relevant data of the patients was collected and analyzed as per designed proforma. Results: Out of 140 cases, majority of the patients were in 41-50 years age group 63 cases (45%), followed by 31-40 years age group 59 cases (42.14%). Most common clinical presentation was heavy menstrual bleeding in 83 cases (59.28%), followed by intermenstrual bleeding and pain in abdomen in 66 cases (47.14%) each. Commonest lesion found was leiomyoma, 83 cases (59.28%), second being dual pathology of adenomyosis with leiomyoma 23 cases (16.42%) followed by adenomyosis, 19 cases (13.57%). Four cases (2.85%) of benign endometrial polyp and endometrial carcinoma each and 1 case of adenomyoma, simple endometrial hyperplasia and endometrial stromal sarcoma, each, were reported. Conclusions: A wide spectrum of histopathological findings, ranging from normal cyclic endometrium to benign pathology and malignancy were seen. In some patients, dual pathologies, incidental findings and occult malignant lesions, which were missed clinically or radiologically, was diagnosed on histopathological examination, thus making it a gold standard for definite diagnosis.

Immunohistochemical expression of B-cell lymphoma 2 gene -Bcl-2 in endometrial carcinoma

Background and objectives: Apoptosis, a process of cell death, is inhibited by the B-cell lymphoma 2 protein, leading to the prolonged survival of cells. Participation of Bcl-2 in starting and advancement of endometrial carcinoma remains inconclusive, with varying results observed. The aims of this study were to assess the frequency of B-cell lymphoma 2 expression in endometrial carcinoma, and to investigate the connection between B-cell lymphoma 2 expression with some clinicopathological parameters. Methods: A retrospective study was carried out for seventy-eight formalin fixed paraffin embedded blocks of total abdominal hysterectomy specimens diagnosed as endometrial carcinoma, which were randomly obtained from a private laboratory and Rizgary teaching hospital laboratory in Erbil city during June 2021-June 2022. In this study, endometrial carcinoma cases were subjected to the utilization of B-cell lymphoma 2 gene, which is a Mouse monoclonal antibody, and its expression was evaluated. Results: The expression of Bcl-2 was observed in 61.5% of the studied cases. The majority (93.6%) of EC cases were of low grade, although Bcl-2 expression was observed at a greater frequency (64.4%) in low-grade endometrial carcinoma, but there was no significant association. Additionally, no statistically significant correlation was found between B-cell lymphoma 2 gene expression and other clinicopathological parameters like, age, myometrial invasion, lympho-vascular invasion, lymph node status and tumor stage. Conclusion: Bcl-2 was expressed in 61.5% of the studied cases with no significant association with any of the variables, additional research is necessary to assess the expression of B-cell lymphoma 2 gene in relation to endometrial carcinoma invasion and metastasis.

Endometrial carcinoma with cervical stromal invasion: Three case reports

BACKGROUND Endometrial cancer is a kind of well-known tumors of female genitourinary system. Cervical stromal invasion is an adverse factor for poor prognosis of endometrial cancer. There is still controversy regarding the use of magnetic resonance imaging (MRI) in the diagnosis of cervical stromal invasion of endometrial cancer. The diagnosis of cervical stromal invasion varies significantly between different observers and institutions. We present a limited case series of the particular pattern of endometrial cancer, which infiltrates the cervical stroma and is often overlooked. CASE SUMMARY We present three cases of endometrial carcinoma with cervical stromal invasion with cancer-free uterine cavity. One patient, a reproductive-aged woman, exhibited irregular menstruation and was diagnosed with endometrial polyps by hysteroscopy and segmental curettage. A MRI scan revealed polypoid nodules within the internal cervical orifice. The other two cases were postmenopausal women who presented with abnormal vaginal bleeding. Hysteroscopy and segmental curettage suggested atypical hyperplasia of the endometrium. MRI scans did not detect any malignant signs in the endometrium. In one case, a non-thickened endometrium was observed, while in another, hyperplasia of the endometrium was seen. Notably, none of these patients had malignant tumors identified in the uterine cavity via MRI scans. However, postoperative pathological results following hysterectomy consistently indicated cervical stromal invasion. CONCLUSION Cervical stromal invasion is easily missed if no cancer is found in the uterine body on MRI. Immunohistochemistry of endoscopic curettage specimens should be conducted to avoid underestimation of the disease.

High-grade Endometrial Carcinoma With Serous and Colorectal Carcinoma-like Components: Unique Morphology in Correlation With Immunohistochemical and Molecular Findings.

Endometrial carcinoma with intestinal differentiation/colorectal carcinoma-like (CRC-like) features is rare with few cases reported to date. Those described are mainly endometrioid carcinomas with intestinal differentiation. We report a case of high-grade endometrial carcinoma with serous and intestinal/CRC-like components. The gross, histologic, immunohistochemical, and molecular features are described for both components of the tumor in the initial diagnostic biopsy and subsequent resection specimen. The diagnosis of primary endometrial carcinoma with serous and CRC-like components is supported by immunohistochemical and molecular findings, as well as clinical workup. The rarity of this phenomenon poses diagnostic challenges. In addition, the literature is reviewed with specific emphasis on the molecular and pathologic features of mixed endometrial carcinomas, including those with intestinal/CRC-like features.

Role of Multiparametric MRI in the Preoperative Evaluation of Endometrial Carcinoma: A Cross-Sectional Study.

Background Endometrial carcinoma (EC) is a major global concern in females throughout the world with increasing incidence in India. Hence, early detection and prompt intervention will reduce morbidity and mortality associated with it. Multiple studies showed a promising role of multiparametric magnetic resonance imaging (mpMRI) in the evaluation and early detection of the disease. In view of the paucity of such studies in the Indian population, we assessed the role of mpMRI in the evaluation of EC by utilizing a 3T MR scanner. Objectives To assess the efficacy of mpMRI in detecting myometrial invasion and locoregional staging in suspected or diagnosed cases of EC. Materials and methods Nineteen cases of EC with mpMRI were included in the study, and 15 of these underwent surgicopathological staging. The preoperative staging was done using the International Federation of Gynecology and Obstetrics (FIGO) 2009 staging system based on mpMRI findings and compared with postoperative FIGO staging. All the data were compiled in a Microsoft Excel (Microsoft® Corp., Redmond, WA) file and analyzed in Statistical Product and Service Solutions (SPSS, version 21.0; IBM SPSS Statistics for Windows, Armonk, NY) using appropriate tools. Results In our study, EC was commonly seen in more than 50-year females with a predominant complaint being postmenopausal bleeding. EC most commonly appeared heterogeneously hyperintense on T2-weighted sequence (T2W) and areas of diffusion restriction on diffusion-weighted imaging (DWI) in all cases. Dynamic contrast-enhanced (DCE) MRI (DCE-MRI) showed mild heterogeneous enhancement in all phases with better delineation of adjacent myometrial infiltration in the equilibrium phase. Diffusion tensor imaging (DTI) parameters had significantly lower values in involved myometrium vis-a-vis uninvolved myometrium. A statistically significant correlation was seen between preoperative mpMRI FIGO staging utilizing T2W, DWI, DCE-MRI, and DTI with surgicopathological FIGO staging. Conclusion mpMRI, particularly T2W, DWI, DCE-MRI, and DTI, yields a significant correlation between MR imaging and histopathological findings in assessing myometrial infiltration and thereby could be helpful in preoperative staging and extent of lymph-nodal dissection.

Morphomolecular Correlation and Clinicopathologic Analysis in Endometrial Carcinoma.

Research groups have identified 4 groups [polymerase epsilon (POLE) mutant, mismatch repair-deficient, p53-abnormal, and no specific molecular profile)] reflecting the Tumor Cancer Genomic Atlas Research Network subgroups in endometrial carcinomas, improving the clinical applicability of molecular classification. We have analyzed the histopathologic and prognostic characteristics of our cases based on the ProMisE classification, supported by growing data on recommended treatment regimens. The study included 118 cases of endometrial carcinoma diagnosed between 2016 and 2020, which underwent mismatch repair and p53 immunohistochemistry. Next-generation sequencing was performed for POLE mutation analysis, dividing the cases into 4 subgroups. The histopathologic and clinical characteristics of these groups were then analyzed statistically. Four cases(3.4%) were classified as POLE mutant, 31 (26.3%) as mismatch repair-deficient, 22 (18.6%) as p53 mutant, and 61 (51.7%) as no specific molecular profile. We categorized 118 patients with endometrial carcinoma into low (n=43), intermediate (n=28), high-intermediate (n=21), high (n=22), and advanced metastatic (n=4) risk groups regardless of the molecular subtypes of their disease. When we reclassified all cases according to the molecular subtypes of endometrial carcinoma only the risk group of 3 (2.5%) cases changed. Using the new algorithm we designed, after narrowing down the number of patients, the microcystic, elongated, and fragmented pattern of invasion was revealed as an independent prognostic factor that reduces overall survival time (hazard ratio: 16.395, 95% CI: 2.140-125.606, P =0.007). In conclusion, using the new algorithm we have designed, and by identifying patients for whom molecular classification could alter risk groups, we observed that molecular tests can be utilized more efficiently in populations with limited economic resources and, in doing so, we discovered a new morphologic marker with prognostic significance.

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.

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.

Comparison of PD-L1, VISTA, LAG-3, and GAL-3 Expressions and Their Relationships to Mismatch Repair Protein and p53 Expression in 529 Cases of Endometrial Carcinoma.

The aim of this study is to evaluate the expressions of programmed death-ligand 1 (PD-L1), V-domain Ig suppressor of T-cell activation (VISTA), lymphocyte activation gene-3 (LAG-3), and galectin-3 (GAL-3), in mismatch repair-deficient (MMRd)/MMR-proficient and abnormal p53 expressing endometrial carcinomas and their relationship with clinical-histopathological features. Patients who underwent surgery for endometrial carcinoma between January 2008 and December 2018 were included in the study. Immunohistochemical analysis of MLH1, PMS2, MSH2, MSH6, p53, PD-L1, VISTA, LAG-3, and GAL-3 was performed on the tissue samples of microarray. A total of 529 patients were included. MMRd and p53-mutant tumors accounted for 31.5% and 11.5% of cases, respectively. PD-L1 and LAG-3 expressions in the MMRd and p53-mutant groups were higher than in the MMR-proficient group (P < 0.001). GAL-3 expression in the MMR-proficient group was statistically higher than in the MMRd and p53-mutant groups (P < 0.001). Mean age, grade, International Federation of Gynecology and Obstetrics stage, lymphovascular invasion, and lymph node metastasis were significantly higher in the p53-mutant group (P < 0.001). In the group with PD-L1 expression, nonendometrioid histologic type, tumor grade, and lymphovascular invasion were significantly higher (P < 0.001). Tumor grade, lymphovascular invasion, lymph node metastasis, and microcystic, elongated and fragmented pattern of invasion were significantly higher in the group with high VISTA expression (P < 0.05). Tumor grade was significantly higher in the group with LAG-3 expression (P < 0.001). Immunohistochemically determined subgroups and PD-L1, VISTA, LAG-3, and GAL-3 expression levels may be useful indicators of molecular features, and clinical outcomes also may have important implications for the development of targeted therapies in endometrial carcinoma.

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.

A prospective study of endometrial histopathology in post-menopausal women in Jharkhand.

Postmenopausal bleeding (PMB) refers to any uterine bleeding in a menopausal women. In the early menopausal years, endometrial hyperplasia, polyps and submucosal fibroids are common etiologies of post menopausal bleeding. The most common cause of postmenopausal bleeding is endometrial atrophy, comprises of 60-80%, while endometrial hyperplasia and endometrial cancer contribute to only 11% of Post menopausal bleeding. The aim of study is to analyses histomorphological pattern of endometrium in patients presenting with post-menopausal bleeding in Jharkhand. 103 postmenopausal women presenting to tertiary center of Jharkhand in 2020-22 with bleeding were subjected to endometrial curettage for histopathology. Analysis is based on morphological criteria to assess endometrium. Endometrial histology is of four categories: Proliferative, Secretory, premalignant and carcinoma. The highest incidence of postmenopausal bleeding was noticed in age group of < 60 years and incidence of malignancy was higher after 57 years of age. The majority of patients had parity between 1 and 3 (78.6%). Malignant & premalignant lesions comprises about 22.3% among that 77.7% were due to benign causes. Among the benign causes of postmenopausal bleeding, proliferative endometrium was the commonest finding. Types of hyperplasia encountered were simple hyperplasia without atypia (6.8%), Complex hyperplasia without atypia (3.9%),Complex hyperplasia with atypia (4.8%) and Simple hyperplasia with atypia (4.8%). 21.4% of cases of postmenopausal bleeding were associated with atrophic endometrium. Secretory endometrium seen in 17.5% of women. Endometrial carcinoma accounted for 12.6% of cases of postmenopausal bleeding. Out of these 69.2% were of endometroid type of endometrial carcinoma, 15.3% were of papillary serous carcinoma and 15.3% had clear cell carcinoma. The mean age of patients with endometrium carcinoma was 62.3 years. All cases of endometrial carcinoma were associated with 1 or more risk factor like diabetes/hypertension/Nulligravida. Proliferative Endometrium was a major cause of postmenopausal bleeding. Among the malignant causes, endometrial adenocarcinoma of endometroid type was most frequent with a lower mean age at presentation than other high grade cancers like papillary serous carcinoma & clear cell 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.

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.

Utility of ER, p53, CEA and Napsin A in Histological Subtyping of Endometrial Carcinoma and Their Correlation with Clinicopathological Prognostic Parameters: Experience from a Referral Institute.

Endometrial Carcinoma (EC) is the most common gynecological cancer with a global incidence of 23.2 per 1 lakh population. Histological subclassification of EC is extremely crucial for the diagnosis, proper management strategies, and prognosis. This study was conducted in a tertiary care institute to analyze the expression pattern of a minimum panel of 4 markers (ER, p53, CEA, Napsin A) with emphasis on their utility in the routine histological subtyping, aberrant expression, and correlation with various clinicopathological parameters. A time-bound cross-sectional observational and analytical study was conducted, which includes cases diagnosed in our laboratory from January 2016 to April 2021. Sixty cases diagnosed as EC during the study period formed the sample cases. The ER was expressed in 85% (53/60) of cases in the current study. Among them, 94% (50/53) were endometrioid endometrial carcinomas (EECs). A negative correlation was found between ER intensity and age (r= -1.48). Of 60 EC cases, 10 (16%) cases expressed p53. The tumors positive for p53 with higher intensity were negative for ER and vice versa. The expression pattern of ER and p53 was statistically significant (P=-0.021). On IHC, 84.6% (11/13) of CEA-positive cases expressed both ER and CEA, suggesting mucinous differentiation. Napsin A was expressed in two cases of EEC, FIGO grade I, and one case of serous carcinoma. An inverse association was found between ER and p53 expression. The CEA is valuable in identifying EEC with mucinous differentiation.

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.