Endometrial Adenocarcinoma Research Articles

The Diagnostic and Prognostic Significance of ARID1A and CD8+ Expression in Endometrial Hyperplasia and Endometrial Endometrioid Adenocarcinoma (Immunohistochemical study)

The Diagnostic and Prognostic Significance of ARID1A and CD8+ Expression in Endometrial Hyperplasia and Endometrial Endometrioid Adenocarcinoma (Immunohistochemical study)

The analysis of hormonal status and vascular and cell proliferation in endometrioid endometrial adenocarcinomas.

Endometrioid endometrial carcinomas (EECs) are the most common malignancies of the uterus. Hormonal dependence of EEC, in relation to biomolecular mechanisms involved in tumor progression, such as angiogenesis and cell proliferation, are aspects that can contribute to improving the prognosis of patients. We analyzed the immunoexpression of markers addressed to steroid hormone receptors [estrogen receptor (ER), progesterone receptor (PR)], angiogenesis [cluster of differentiation (CD)105∕endoglin] and cell proliferation (Ki-67) in 50 EECs related to the histopathological prognostic criteria of the lesions. In this study, the ER and PR scores were higher in low grade and early stages EEC, the statistical aspects being variable. The CD105 microvessel density and the Ki-67 proliferation index were superior in high grade and advanced stages EEC, the statistical aspects being significant or at the limit of significance. The ER∕PR and CD105∕Ki-67 immunomarker groups indicated a positive linear intragroup relation and a negative linear intergroup relation, suggesting the presence of synergistic and antagonistic molecular mechanisms of tumor endometrial control that can be used to stratify patients for targeted therapy.

Mesonephric-Like Adenocarcinoma of the Endometrium: Review of the Literature and Practical Diagnostic Recommendations

Abstract Mesonephric-like adenocarcinomas are endometrial and ovarian neoplasms of müllerian origin with morphologic, immunophenotypic, and molecular evidence of mesonephric-type transdifferentiation, as well as considerable homology with endometrioid tumors. First described in 2016, mesonephric-like adenocarcinomas are morphologically indistinguishable from “true” mesonephric adenocarcinomas of the uterine cervix, but the latter are distinguished by (1) primary localization to the cervical wall, (2) frequent association with mesonephric remnants, and (3) in some cases, lack of mucosal involvement. Despite an overall low-grade morphology, mesonephric-like adenocarcinoma follows an aggressive clinical course, characterized by frequent and early recurrences, most often in the lung. Accordingly, accurate distinction of mesonephric-like adenocarcinoma from morphologic mimics—especially low-grade endometrioid adenocarcinoma—is critical. However, available evidence indicates that endometrial mesonephric-like adenocarcinomas are significantly underdiagnosed, likely due to their relative novelty, rarity, and considerable overlap with endometrioid neoplasia. Prospective recognition of characteristic morphologic features, a low threshold for application of diagnostic immunohistochemistry, and judicious use of molecular studies will permit accurate diagnosis in almost all cases.

Perspectives in Endometrial Pathology

When you feel life at crossroads, you need higher perspective view. —Toba Beta in My Ancestor Was an Ancient Astronaut After the publication of the integrated genomic characterization of endometrial carcinoma by The Cancer Genome Atlas project in 2013, the subclassification of endometrial carcinoma has gained much more attention than previously. Like in many other areas in our profession, we are at a crossroad where molecular information is changing diagnostic practice. In this issue of AJSP: Reviews & Reports, Drs Bosse and Köbel share their thoughts in 2 separate articles on how they envision the future with the added complexity of molecular information on top of standard anatomical pathology. Both agree on the value of molecular information and certain basic principles (eg, the defining nature of key oncogenic alterations such as POLE mutations or mismatch repair deficiency). However, they have different views of how to integrate molecular subtype information with standard histomorphology: with one approach being more integrated versus more stand-alone. Although standard histomorphology and molecular subtype strongly correlate, sometimes they contradict each other. At this point, someone, either the pathologist or the oncologist, has to adjudicate. This decision is not generalizable and is dependent on the context of the specific histomorphology and the specific molecular result, and who would be better posed to make that decision than a pathologist? Designation of an endometrial carcinoma to a specific category increasingly conveys prognostic, predictive, and germline information; accurate and reproducible diagnosis is mandatory. Integration of the traditional and molecular parameters is critical to ensure a relevant taxonomy of endometrial pathology with the ultimate goal of improving the outcomes in women's health. Drs Chapel and Park next provide a comprehensive contemporary review on mesonephric-like adenocarcinomas. Although various explanations of the etiology of this tumor type have been discussed, the authors state that endometrial mesonephric-like adenocarcinomas likely arise through mesonephric-type transdifferentiation from endometrioid carcinomas. They describe the morphological, immunohistochemical, and molecular features of this tumor type and give recommendations for the diagnostic approach. They provide cogent clinical reasons to warrant distinguishing this tumor type from endometrioid carcinomas. The entity of undifferentiated endometrial carcinoma and its related dedifferentiated carcinoma has gained substantial interest over the last years. Drs Y.-S. Lee and C.-H. Lee take us a step further by emphasizing the importance of key molecular alterations in the SWI/SNF (SWItch/sucrose non-fermentable) pathway as a defining feature for cases that are associated with a devastating clinical outcome. Again, ancillary molecular testing enables a more homogeneous diagnosis, which clarifies the poor response to standard therapy and calls for more research in experimental models to find new ways to treat patients with this molecularly defined entity. The synchronous involvement of the endometrium and ovary/fallopian tube by carcinoma is a regular diagnostic challenge. Drs Singh et al provide a new perspective by separately discussing this issue for serous and endometrioid histotypes. Although questions remain, systematically the authors list criteria and provide reporting strategies for different scenarios based on current understanding. Perhaps, the integration of molecular subtypes particularly for endometrioid histotypes can further aid in risk stratification of these patients. We are increasingly receiving requests from obstetrician-gynecologist for CD138 immunohistochemistry in the context of infertility. Dr S. Lee reviews the current data: although there is some indication that diagnosis and successful treatment of chronic endometritis may positively affect pregnancy outcome, a single randomized clinical trial did not confirm this. Yet, another trial is ongoing, which uses ≥5 CD138+ plasma cells per 10 mm2 as cutoff for chronic endometritis. But the results are pending. Until then, there is no indication for routine use of CD138 or other immunohistochemistry to detect plasma cells in the context of infertility and certainly not in others.

Cutaneous Metastsis of An Endometrioid Adenocarcinoma to The Face

Background: Cutaneous metastasis is uncommon in endometrial cancer. Recurrence to the skin has been demonstrated to occur in the abdomen, pelvis and scalp. This is the first case presented of a cutaneous metastasis to the face. Case: A 60-year-old Nepalese woman stage 1A grade 1 endometrial adenocarcinoma experienced metastasis to her external iliac lymph node 15 months after her initial presentation. After the recurrence was treated with chemotherapy, she experienced cutaneous metastasis of her endometrial carcinoma to her face 34 months after her initial surgery. The patient passed away 3 months after. Conclusion: Endometrial adenocarcinoma can metastasize to the face and is associated with a poor prognosis

12-O-Tetradecanoylphorbol 13-acetate promotes proliferation and epithelial-mesenchymal transition in HHUA cells cultured on collagen type I gel: A feasible model to find new therapies for endometrial diseases.

HHUA endometrial adenocarcinoma cells aggregated into spheroids when cultured on collagen type I gels. 12-O-Tetradecanoylphorbol 13-acetate, a PKC activator, disassembled the spheroids through epithelial-mesenchymal transition and increased their proliferation rate, while inducing cell death under monolayer culture conditions. These unusual behaviors of endometrial epithelial cells with collagen fibers could be a target for the treatment of some endometrial diseases.

Role of MRI in pre-operative staging of endometrial cancer: A diagnostic accuracy study

Endometrial cancer (EC) is a commonly occurring cancer among post-menopausal women. Pre-treatment imaging of the extent of disease can influence the decisions in the management of EC. MRI with its diffusion weighted (DW) images can help in better depiction of the primary tumour, its local extension and extrauterine spread to the peritoneum and lymph nodes. This study was conducted to know the role of MRI for pre-operative staging of endometrial cancer and as a guide for pelvic lymph nodal dissection.It was a descriptive cross-sectional study conducted at a tertiary care hospital patients diagnosed with primary endometrial adenocarcinoma on biopsy. Patients with advanced disease requiring chemotherapy prior to surgery were excluded. Fifty consecutive patients were subjected to MRI Pelvis with abdominal screening in the week preceding definitive surgery, Findings from imaging were compared with final histopathology for concurrence on tumour size, depth of myometrial invasion, presence of adnexal, nodal and cervical stromal involvement.Majority of the patients in this study were post-menopausal women. Sensitivity of MRI for staging of Endometrial Carcinoma in this study was 91.84% and Accuracy was 90%. When compared to HPE for lymph node positivity, MRI had sensitivity of 100%, specificity of 97.87%, PPV of 75%, NPV of 100% and accuracy of 98%.Pre-operative MRI in the week prior to the planned surgery can help in accurately staging the endometrial carcinoma in terms of myometrial infiltration, cervical stromal infiltration as well as pelvic lymph nodal involvement.

Effect of sentinel lymph node isolated tumor cells on recurrence free survival in patients with mismatch repair proficient vs. deficient stage I/II endometrioid endometrial adenocarcinoma (173)

Objectives: To assess associations between mismatch repair (MMR) status and recurrence-free survival (RFS) among early-stage endometrial cancer patients with and without isolated tumor cells (ITCs). Methods: We conducted a multi-institution, retrospective study of women with stage I/II endometrial cancer with endometrioid histology who underwent surgical staging with sentinel lymph node (SLN) mapping with or without completing the lymphadenectomy between 2016 and 2021. SLN mapping was performed following the NCCN SLN mapping guidelines. ITC patients and matched controls were identified through electronic medical records using keyword search. Patients were excluded if they had evidence of micro-or macro-metastases in any lymph node (LN). Categorical variables were analyzed using the Chi-square test and continuous variables were analyzed with Student’s t-test and the two-proportion Z-test. Kaplan–Meier method and log-rank tests were used for survival analysis. Results: Among 234 patients, 38 were found to have ITCs. The majority had grade 1 (82.1%), stage IA (67.0%), endometrioid adenocarcinoma. Overall, 22.2% of tumors were MMR deficient by immunohistochemistry. Patients with ITCs were more likely to demonstrate > 50% myometrial invasion (24.5% vs 52.5%, p=<0.001) and were more likely to receive adjuvant radiation therapy (14.8% vs 42.1%, p<0.001) and/or chemotherapy (2.6% vs 23.7%, p<0.001). Grade (p=0.923) and MMR status (p=0.850) were not significantly different between patients with ITCs and those with LN-negative disease. The Median follow-up time was 27 months. Overall, 11 patients we re diagnosed with recurrence (4.7%). The recurrence rate for patients with LN-negative disease was 4.6% (9/196) and the recurrence rate for ITC positive patients was 5.3% (2/38) (p=0.842). The 3-year RFS was 96% in patients with LN-negative disease and 88% in patients with ITC positive disease (log-rank p=0.712). Recurrence rates were comparable among patients with MMR proficient tumors, regardless of ITC status (LN-negative: 3.3% vs ITC-positive: 3.4%; p=0.975). This was also true among patients with MMR deficient tumors (LN-negative: 9.3% vs ITC-positive: 11.1%,p=0.175). RFS was not different between LN-negative and ITC-positive patients with MMR proficient tumors (log-rank p=0.846) as well as between LN-negative and ITC-positive patients with MMR deficient tumors (log-rank p=0.790). Conclusions: These preliminary data suggest that the presence of ITCs does not impact RFS in early-stage endometrial cancer patients with MMR proficient or MMR deficient tumors. However, a longer follow-up time and a larger sample size are needed to better explore the relationship between the presence of ITCs and tumor molecular characterization. Objectives: To assess associations between mismatch repair (MMR) status and recurrence-free survival (RFS) among early-stage endometrial cancer patients with and without isolated tumor cells (ITCs). Methods: We conducted a multi-institution, retrospective study of women with stage I/II endometrial cancer with endometrioid histology who underwent surgical staging with sentinel lymph node (SLN) mapping with or without completing the lymphadenectomy between 2016 and 2021. SLN mapping was performed following the NCCN SLN mapping guidelines. ITC patients and matched controls were identified through electronic medical records using keyword search. Patients were excluded if they had evidence of micro-or macro-metastases in any lymph node (LN). Categorical variables were analyzed using the Chi-square test and continuous variables were analyzed with Student’s t-test and the two-proportion Z-test. Kaplan–Meier method and log-rank tests were used for survival analysis. Results: Among 234 patients, 38 were found to have ITCs. The majority had grade 1 (82.1%), stage IA (67.0%), endometrioid adenocarcinoma. Overall, 22.2% of tumors were MMR deficient by immunohistochemistry. Patients with ITCs were more likely to demonstrate > 50% myometrial invasion (24.5% vs 52.5%, p=<0.001) and were more likely to receive adjuvant radiation therapy (14.8% vs 42.1%, p<0.001) and/or chemotherapy (2.6% vs 23.7%, p<0.001). Grade (p=0.923) and MMR status (p=0.850) were not significantly different between patients with ITCs and those with LN-negative disease. The Median follow-up time was 27 months. Overall, 11 patients we re diagnosed with recurrence (4.7%). The recurrence rate for patients with LN-negative disease was 4.6% (9/196) and the recurrence rate for ITC positive patients was 5.3% (2/38) (p=0.842). The 3-year RFS was 96% in patients with LN-negative disease and 88% in patients with ITC positive disease (log-rank p=0.712). Recurrence rates were comparable among patients with MMR proficient tumors, regardless of ITC status (LN-negative: 3.3% vs ITC-positive: 3.4%; p=0.975). This was also true among patients with MMR deficient tumors (LN-negative: 9.3% vs ITC-positive: 11.1%,p=0.175). RFS was not different between LN-negative and ITC-positive patients with MMR proficient tumors (log-rank p=0.846) as well as between LN-negative and ITC-positive patients with MMR deficient tumors (log-rank p=0.790). Conclusions: These preliminary data suggest that the presence of ITCs does not impact RFS in early-stage endometrial cancer patients with MMR proficient or MMR deficient tumors. However, a longer follow-up time and a larger sample size are needed to better explore the relationship between the presence of ITCs and tumor molecular characterization.

Tumor immune microenvironment and implications for progression and survival in patients with recurrent endometrial cancer (182)

Objectives: The immunologic response to cancer influences disease progression and survival in ways that are not yet completely understood. The objective of this analysis was to understand markers of immune exhaustion and mismatch repair within the tumor immune microenvironment in patients with recurrent endometrial cancer. Methods: We identified patients matched with primary and recurrent endometrial adenocarcinoma at a single high-volume academic medical center. Histologic slides were reviewed to confirm the diagnosis of primary and recurrent cancer, and formalin-fixed paraffin-embedded tissue blocks were requested from archives. Immunohistochemistry (IHC) was performed using antibodies against CD3 and immune exhaustion markers (PD1, PDL1, CTLA4, TIM3, and TIGIT) to quantify the number of tumor-infiltrating lymphocytes (TILs). Peritumoral lymphocytes (PTLs) were evaluated in a semi-quantitative manner. Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS), and the log-rank test was used to compare between groups. Conclusions: Among patients with endometrial cancer who ultimately develop recurrent disease, the number of TILs and expression of immune exhaustion markers at initial diagnosis are not associated with PFS but are associated with OS. Specifically, the higher number of lymphocytes and increased expression of exhaustion markers PD1, PDL1, and TIGIT at the time of initial diagnosis are associated with decreased OS. Further work is needed to determine the prognostic value of immune exhaustion markers for patients who develop recurrent endometrial cancer. Objectives: The immunologic response to cancer influences disease progression and survival in ways that are not yet completely understood. The objective of this analysis was to understand markers of immune exhaustion and mismatch repair within the tumor immune microenvironment in patients with recurrent endometrial cancer. Methods: We identified patients matched with primary and recurrent endometrial adenocarcinoma at a single high-volume academic medical center. Histologic slides were reviewed to confirm the diagnosis of primary and recurrent cancer, and formalin-fixed paraffin-embedded tissue blocks were requested from archives. Immunohistochemistry (IHC) was performed using antibodies against CD3 and immune exhaustion markers (PD1, PDL1, CTLA4, TIM3, and TIGIT) to quantify the number of tumor-infiltrating lymphocytes (TILs). Peritumoral lymphocytes (PTLs) were evaluated in a semi-quantitative manner. Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS), and the log-rank test was used to compare between groups. Conclusions: Among patients with endometrial cancer who ultimately develop recurrent disease, the number of TILs and expression of immune exhaustion markers at initial diagnosis are not associated with PFS but are associated with OS. Specifically, the higher number of lymphocytes and increased expression of exhaustion markers PD1, PDL1, and TIGIT at the time of initial diagnosis are associated with decreased OS. Further work is needed to determine the prognostic value of immune exhaustion markers for patients who develop recurrent endometrial cancer.

Functional PTEN mutations in progestin-resistant de novo endometrial intraepithelial neoplasia (119)

<b>Objectives:</b> Endometrial intraepithelial neoplasia (EIN), including simple hyperplasia and complex hyperplasia with atypia (CAH), is a precursor lesion for endometrial adenocarcinoma. Not all patients with EIN are eligible for or choose to have a hysterectomy and are typically treated with progestin. Depending on EIN classification and covariates like obesity, 25-50% of cases fail to respond to progestin therapy. We hypothesized that non-responders might have mutations in <i>PTEN</i> that affect function but not expression. <b>Methods:</b> This is a retrospective case-control study of 49 patients who had <i>de novo</i> endometrial biopsies with EIN (41 CAH and eight simple hyperplasia). Included cases required diagnoses confirmed by two pathologists and a history of oral or IUD progestin therapy. All the cases had at least 3-6 months of follow-up biopsies. Regions of interest containing EIN were sampled for DNA analysis using histologic sections and the commercially available GeneTrails^c solid tumor panel. Protein expression was measured in serial sections by Nanostring immunolabeling and GeoMx spatial profiling. Data were analyzed by Chi-square and unsupervised clustering with adjusted p-values. <b>Results:</b> Clinical follow-up revealed that 24 patients were progestin responders (eight simple hyperplasia and 16 CAH), and 25 were progestin non-responders (all with CAH). Those who did not respond to progestin either progressed to adenocarcinoma by three months or had persistent hyperplasia by six months. <i>PTEN</i> mutations above the variable allele frequency were identified in 19/25 of the progestin non-responders and 2/16 of the progestin responders yielding a likelihood ratio of 6 (2-23, p<0.001). Nanostring immunolabeling revealed no difference in <i>PTEN</i> expression between groups. <b>Conclusions:</b> Although there are no significant differences in <i>PTEN</i> expression in progestin non-responders compared with progestin responders for patients with EIN, there is a significantly increased frequency of <i>PTEN</i> functional mutations in the non-responders. This data suggests that genomic information, specifically <i>PTEN</i> mutations, predicts treatment response to progestin in EIN and has the potential to guide treatment decisions.

Epigenetic mismatch repair deficiency in endometrioid endometrial cancer correlates with poor outcome (385)

Epigenetic mismatch repair deficiency in endometrioid endometrial cancer correlates with poor outcome (385)

MLH1 hypermethylation predicts poor outcomes with pembrolizumab in recurrent endometrial cancer (087)

Objectives: To determine response rate, recurrence-free survival, and overall survival to pembrolizumab in recurrent endometrial adenocarcinomas based upon the classification of mismatch repair (MMR) deficiency. Methods: A retrospective study was conducted among all women with recurrent endometrial adenocarcinomas treated with single-agent pembrolizumab at our institution from 2017 to 2021. Cases were included if complete mismatch repair data were available and were categorized based upon MMR status – germline Lynch Syndrome mutation (gLS), somatic Lynch Syndrome mutation (sLS), or MLH1 promoter hypermethylation (hMLH1). Clinical and pathologic data were abstracted by chart review and included patient demographics, tumor characteristics, recurrence date, and treatment. Continuous predictors were compared between groups using two-sample t-tests. Ordinal predictors such as stage and grade were compared using Wilcoxon rank-sum tests. Categorical predictors were compared using Fisher’s exact tests due to small counts. Unadjusted differences in survival were compared with log-rank tests and visualized with Kaplan-Meier curves. Cox proportional hazards models were used to compare differences in survival between groups after adjusting for BMI. All statistical tests were conducted in R v3.5.1 with an alpha level of 0.05. Results: Eighteen patients were categorized into two groups based upon results of tumor MMR testing and germline genetic testing: gLS/sLS (n = 6, 33.3%) or hMLH1 (n = 12, 66.7%). The hMLH1 patients had a higher mean BMI than gLS/sLS patients (40.9 vs 28.5, p = 0.003). Demographic and tumor characteristics were otherwise well-matched between groups. Median follow-up was 9.45 months with a response rate of 55.6%. When stratified by MLH1 hypermethylation status, response rate was 83.3% in gLS/sLS patients and 41.7% in hMLH1 patients, though this did not reach statistical significance (p = 0.152). Recurrence-free survival (RFS) was significantly decreased among hMLH1 patients (p = 0.031). Similarly, overall survival (OS) was significantly decreased for these patients (p = 0.037), as shown in Figure 1. Objectives: To determine response rate, recurrence-free survival, and overall survival to pembrolizumab in recurrent endometrial adenocarcinomas based upon the classification of mismatch repair (MMR) deficiency. Methods: A retrospective study was conducted among all women with recurrent endometrial adenocarcinomas treated with single-agent pembrolizumab at our institution from 2017 to 2021. Cases were included if complete mismatch repair data were available and were categorized based upon MMR status – germline Lynch Syndrome mutation (gLS), somatic Lynch Syndrome mutation (sLS), or MLH1 promoter hypermethylation (hMLH1). Clinical and pathologic data were abstracted by chart review and included patient demographics, tumor characteristics, recurrence date, and treatment. Continuous predictors were compared between groups using two-sample t-tests. Ordinal predictors such as stage and grade were compared using Wilcoxon rank-sum tests. Categorical predictors were compared using Fisher’s exact tests due to small counts. Unadjusted differences in survival were compared with log-rank tests and visualized with Kaplan-Meier curves. Cox proportional hazards models were used to compare differences in survival between groups after adjusting for BMI. All statistical tests were conducted in R v3.5.1 with an alpha level of 0.05. Results: Eighteen patients were categorized into two groups based upon results of tumor MMR testing and germline genetic testing: gLS/sLS (n = 6, 33.3%) or hMLH1 (n = 12, 66.7%). The hMLH1 patients had a higher mean BMI than gLS/sLS patients (40.9 vs 28.5, p = 0.003). Demographic and tumor characteristics were otherwise well-matched between groups. Median follow-up was 9.45 months with a response rate of 55.6%. When stratified by MLH1 hypermethylation status, response rate was 83.3% in gLS/sLS patients and 41.7% in hMLH1 patients, though this did not reach statistical significance (p = 0.152). Recurrence-free survival (RFS) was significantly decreased among hMLH1 patients (p = 0.031). Similarly, overall survival (OS) was significantly decreased for these patients (p = 0.037), as shown in Figure 1.

An Evaluation of the Immunohistochemical Expression of Mismatch Repair Proteins (MSH2, MSH6, MLH1, and PMS2) in Prostate Adenocarcinoma.

Background and objectiveMismatch repair (MMR) proteins are an integral part of the cell cycle, and they play an important role in the genomic stability of the microsatellite complex. Microsatellite instability (MSI) is associated with Lynch and multi-tumor syndromes. Identifying patients with Lynch syndrome is essential for screening, early detection, and surveillance of other Lynch syndrome-associated tumors. The role of MMR deficiency is well known in colorectal and endometrial adenocarcinoma. However, the role of MMR deficiency in prostatic adenocarcinoma is a matter of controversy. A few studies have been published to analyze the association between MMR deficiency and prostatic adenocarcinoma. In this study, we used immunohistochemistry to look into the expression of four MMR proteins in prostatic adenocarcinoma: MSH2, MSH6, MLH1, and PMS2.MethodologyThis was a cross-sectional descriptive study involving 74 cases of acinar prostatic adenocarcinoma, diagnosed with hematoxylin & eosin (H&E), over a period of six months between December 2021 and May 2022 at the Chughtai Institute of Pathology in Lahore, Pakistan. We performed the immunohistochemical (IHC) analysis and interpretation of four antibodies, i.e., MSH2, MSH6, MLH1, and PMS2.ResultsIn our study, the age of the patients ranged from 50 to 98 years, with a mean age of 67.99 ± 9.59 years. The specimens were collected through transurethral resection of the prostate (TURP), transurethral vaporization of the prostate (TVP), core biopsy, and radical prostatectomy. Isolated loss of each MSH2 and PMS2 was noted in nine cases (12.20%) and MSH6 in two cases (2.70%). There was no loss noted for MLH1. Furthermore, simultaneous loss of MSH2/MSH6 was observed in one case (1.35%).ConclusionOur study findings revealed a low frequency of IHC expression of MMR proteins, especially the concurrent loss of paired MMR proteins. However, prostatic adenocarcinoma is associated with the isolated loss of MMR proteins. Thus, the present study does not warrant reflex testing/screening in every case of prostatic adenocarcinoma, because of its low frequency, which is probably suggestive of its sporadic pattern.

Safety of ovarian preservation for premenopausal patients with FIGO stage I grade 2 and 3 endometrioid endometrial adenocarcinoma

ObjectiveTo investigate the utilization and outcomes of ovarian preservation for premenopausal patients with International Federation of Gynecology and Obstetrics (FIGO) stage I grade 2 and 3 endometrioid endometrial carcinoma undergoing...

Endometrial Adenocarcinoma with Pattern of Invasion Resembling Adenoma Malignum

Endometrial adenocarcinoma with a glandular invasion pattern resembling adenoma malignum of cervix is a deceptively benign and highly differentiated form of endometrioid adenocarcinoma which can be resistant to radiation therapy and exhibit a deep invasion pattern. We report a 57-year-old female who was a biopsy-proven case of FIGO grade 2 endometrial adenocarcinoma with 4 cm cervical involvement, who underwent whole pelvic radiation therapy followed by hysterectomy. Her hysterectomy sections revealed conventional endometrioid adenocarcinoma with a deceptively bland pattern of well-spaced, branching glands with myometrial invasion up to 90%. Extensive lymphovascular space invasion was identified and cervical stroma was involved. Immunohistochemistry was consistent with an endometrial origin. The final diagnosis was endometrial adenocarcinoma with adenoma malignum pattern of invasion. It is not clear whether the gland morphology was due to radiation treatment however, the widespread and extensive invasion makes it imperative to recognize that these patients need to be vigilantly followed up. It is important to recognize this entity because these deeply invasive and benign appearing glands can be resistant to the conventional approach of radiation treatment and highlights the fact that the patient needs to be cautiously staged and accordingly treated. Keywords: Endometrial adenocarcinoma; Minimal deviation; Adenoma malignum; Uterus; Pelvic radiotherapy

DSCAM-AS1 Long Non-Coding RNA Exerts Oncogenic Functions in Endometrial Adenocarcinoma via Activation of a Tumor-Promoting Transcriptome Profile.

Accumulating evidence suggests that lncRNA DSCAM-AS1 acts tumor-promoting in various cancer entities. In breast cancer, DSCAM-AS1 was shown to be the lncRNA being most responsive to induction by estrogen receptor α (ERα). In this study, we examined the function of DSCAM-AS1 in endometrial adenocarcinoma using in silico and different in vitro approaches. Initial analysis of open-source data revealed DSCAM-AS1 overexpression in endometrial cancer (EC) (p < 0.01) and a significant association with shorter overall survival of EC patients (HR = 1.78, p < 0.01). In EC, DSCAM-AS1 was associated with endometrial tumor promotor gene PRL and with expression of ERα and its target genes TFF1 and PGR. Silencing of this lncRNA by RNAi in two EC cell lines was more efficient in ERα-negative HEC-1B cells and reduced their growth and the expression of proliferation activators like NOTCH1, PTK2 and EGR1. DSCAM-AS1 knockdown triggered an anti-tumoral transcriptome response as revealed by Affymetrix microarray analysis, emerging from down-regulation of tumor-promoting genes and induction of tumor-suppressive networks. Finally, several genes regulated upon DSCAM-AS1 silencing in vitro were found to be inversely correlated with this lncRNA in EC tissues. This study clearly suggests an oncogenic function of DSCAM-AS1 in endometrial adenocarcinoma via activation of a tumor-promoting transcriptome profile.

P-301 Exome sequencing reveals novel candidate variants for endometriosis and endometrial serous adenocarcinoma in a single family having multiple affected members

Abstract Study question Could genetic evaluation of a family, having multiple affected members with endometriosis, contribute to identifying novel rare variants for the missing heritability of the disease? Summary answer Two novel genetic variants one in each of TNFRSF1B and GEN1 genes detected only in all affected family members, suggesting potential new biomarkers forendometriosis. What is known already Endometriosis is an estrogen-dependent, chronic inflammatory disease that affects 10% of women during the reproductive ages. Despite the estimated 50% heritability for the condition, only 26% was associated with common genetic variants through GWAS studies. The necessity of identifying rare variants for the missing heritability is implicated in the literature. In this respect, only one familial study has suggested novel candidate variants utilizing whole exome sequencing (WES). Study design, size, duration A single family having 4 women diagnosed with endometriosis out of 6 were recruited for genetic delineation utilizing whole exome sequencing (WES). The average follow-up period of the patients were five years. Participants/materials, setting, methods Total of 6 women from the same family. Four women with endometriosis were diagnosed. WES was performed on these 3 women with endometriosis utilizing the Twist Core Exome Target Capture and Enrichment Kit on the Illumina Nextseq 550 platform with 50X coverage. Bioinformatics analyses along with variant prioritization at MAF &amp;lt;1% for all normal populations were performed on Genomize SEQ platform. Candidate genes were subjected to confirmation by Sanger sequencing followed by familial segregation. Main results and the role of chance All endometriosis patients presented with dysmenorrhea. Additionally, one of them reported having dyschezia, one had chronic pelvic pain and the other patient complained having dyspareunia. The 3 patients who underwent WES analysis were also under treatment for endometriosis related infertility. 2 out of these 3 patients had a positive history for endometriosis surgery and presented with recurrent endometriomas. Novel heterozygous missense variants one in each of TNFRSF1B and GEN1 genes were determined in all affected members, while a novel heterozygous missense variant in CRABP1 was detected only in daughters descending from the mother with cancer history. All variants were predicted to be deleterious by in silico tools Limitations, reasons for caution Our findings are limited to the family of interest and needs to be replicated in larger cohorts. Designation of the novel findings as causative mutations, functional validations need to be performed. Wider implications of the findings The novel genetic variants detected will help in providing genetic counseling to the family. Our findings, when replicated in larger cohorts and validated functionally, will provide significant contribution to the elucidation of the molecular mechanisms of the pertinent conditions. Trial registration number not applicable

Fertility sparing approach in young women with endometrial cancer

The incidence of endometrial cancer in young women is increasing, especially in developed countries. Although it is predominantly a disease of peri- and postmenopausal women, there is an absolute increase in younger women of childbearing age who, with today's lifestyle and pushing back maternal needs, do not have fulfilled reproductive plans. About 67% of cancers are diagnosed in the early stages. For these women, fertility-preserving procedures can be considered until reproductive plans are fulfilled. Subsequently, however, definitive management is appropriate even in the absence of carcinoma. This article discusses the most common gynecologic pelvic cancer, endometrial adenocarcinoma, and the possibility of fertility-preserving procedures.

Anévrisme de la veine cave inférieure : à propos d'un cas

Venous aneurysms in general, and of the inferior vena cava in particular (IVC), are rarely reported in the literature because they are generally asymptomatic and detected incidentally following complications such as thrombosis and pulmonary embolism, an Inferior vena cava (IVC) aneurysm is detected by imaging examinations performed for other causes. We report a case of IVC aneurysm classified as type I according to Gradman and Steinberg discovered incidentally during a follow-up CT scan in an asymptomatic woman followed for endometrial adenocarcinoma treated 6 years ago.

Abstract 5125: Biological and clinical value of OCT4A/SPP1C axis in endometrial and lung adenocarcinoma

Abstract Background: It is largely unclear whether octamer-binding transcription factor 4A (OCT4A, OCT3/4A) functions physiologically or pathologically in adult somatic tissues and related cancers. We have recently identified OCT4A translation in a human cancer cell subpopulation that might exacerbate cell migration and invasion. Here, we focus on biological and clinical features of OCT4A and its relationship with secreted phosphoprotein 1(SPP1), which is strongly related to the malignant progression of numerous tumors. Methods: RT-PCR or qPCR analysis was used to identify full-length spliced forms of OCT4A and SPP1 transcripts in non-tumor and tumor human cells. An OCT4A-FLAG-tagged genomic transgene identified OCT4A-positive cancer cells. Cell-ablation of OCT4A-positive cells using promoter-driven diphtheria toxin A was used to examine the potential role of OCT4A in lung and endometrial adenocarcinoma cells. OCT4A and SPP1 transcripts in early-stage lung adenocarcinoma (stage I, fifty-eight cases) were analyzed and compared with pathohistological and prognostic features. Results: We found that OCT4A and SPP1C are co-expressed in highly aggressive human lung and endometrial adenocarcinoma cell lines but not in mesothelioma or non-tumor cell lines. Ablation of OCT4A-positive cells significantly decreased cancer-cell migration and SPP1C mRNA levels. The OCT4A/SPP1C axis was found in primary, early-stage, lung adenocarcinomas, and all four cases of recurrence and/or metastasis out of 58 cases were included in the OCT4A and SPP1C positive group. Conclusions: Co-expression of OCT4A and SPP1C may correlate with human cancer cell migration and the OCT4A/SPP1C axis may have a prognostic value in high-risk, early-stage lung adenocarcinomas.