Expression and clinical significance of KDM5A, KDM5B, and FOXO1 in endometrial cancer.

There is growing evidence that the KDM5 family of histone demethylases plays a causal role in human cancer. However, few studies have been reported on the KDM5 family in endometrial carcinoma (EC). Moreover, it was found that there was some correlation between the KDM5 family and FOXO1 in EC. The current study was performed to explore the expressions of KDM5A, KDM5B, and FOXO1 in endometrioid adenocarcinoma detected by immunohistochemistry; paracancer endometrium, simple hyperplastic endometrium, and normal endometrium were used as control groups to explore the possible diagnostic value of KDM5A and KDM5B expression in endometrioid adenocarcinoma, with the aim of evaluating the potential of this marker in predicting the prognosis of endometrioid adenocarcinoma.

Sister Mary Joseph Syndrome: A Report of a Rare Case.

The Sister Mary Joseph syndrome is characterized by cutaneous metastases localized at the umbilical level. It is a rare clinical sign estimated to occur in 1%-3% of patients with abdominopelvic cancer. The most common histology is adenocarcinoma (75% of cases). The presence of this nodule is often indicative of a poor prognosis, with average survival estimated at two to 11 months without treatment. We report the clinical case of Sister Mary Joseph syndrome in a 50-year-old woman who had been followed for three years for endometrioid adenocarcinoma of the endometrium. The diagnosis was established via umbilical biopsy after a computed tomography scan revealed the presence of an umbilical nodule. The patient is currently undergoing a palliative chemotherapy regimen.

Simultaneous Endometrial Cancer with Extensive Pelvic and Vulvar Endometriosis: A Case Report.

Background: Endometrial cancer represents the most prevalent malignant genital tract neoplasm in high-income countries and is the second most common cancer worldwide following cervical cancer. Endometriosis is a benign condition wherein endometrial glands and stroma are found outside the uterine cavity. Case Presentation: During a routine care and ultrasound examination of the uterus and adnexa of a 64-year-old woman, an increased endometrial thickness (22 mm) was noted. In 2023, according to ultrasound report, the patient underwent diagnostic curettage with immunohistochemistry, revealing a pathological diagnosis of endometrial cancer (endometrioid adenocarcinoma) with positive staining for p16, estrogen receptor (ER), and vimentin. Subsequently, after one week, she underwent complete surgical staging. Extensive superficial endometriosis disseminated in the pelvis and vulva was noted during surgery and preoperative examinations. Final pathology confirmed a well-differentiated typical endometrioid carcinoma (grade 1) with 40% myometrial invasion and positive lymphovascular invasion. The patient was considered to be at stage 1A. Conclusion: Despite some studies suggesting an unclear association between endometriosis and endometrioid or clear-cell ovarian cancers, the correlation between endometriosis and endometrial cancer and its prognosis remains ambiguous. Additionally, although infertility has been linked to both endometrial cancer and endometriosis in various studies, the presented case exhibited no signs of infertility. Extensive pelvic endometriosis with vulvar involvement was present, yet the patient did not exhibit any symptoms. This is in contrast to the typical initial manifestation of endometrial cancer, which is abnormal uterine bleeding. The patient's condition was incidentally detected through routine care due to an abnormal increase in endometrial thickness, prompting this presentation.

Comparison of survival and complications between minimally invasive and open staging surgeries in non-endometrioid endometrial cancer.

OBJECTIVE: This study aimed to compare survival and complications between minimally invasive surgery and open surgery and evaluate related risk factors in patients with non-endometrioid endometrial cancer. METHODS: Clinicopathologic characteristics; survival outcomes; complications; and prognostic factors associated with progression-free survival and overall survival were compared among patients with non-endometrioid endometrial cancer who underwent primary staging surgery using laparoscopic, robotic, or open abdominal surgery (2004-2017). RESULTS: In total, 91 patients were included: 41 and 50 underwent minimally invasive surgery and open surgery, respectively. The minimally invasive surgery and open surgery groups showed similar progression-free survival (5-year progression-free survival rate, 58.7 % vs. 58.5 %; P = .925) and overall survival (5-year overall survival rate, 73.6 % vs. 80.3 %; P = .834). Intraoperative (7.2 % vs. 6.0 %; P = .111) and postoperative surgical complications (14.6 % vs. 26.0 %; P = .165) were similar between the groups. However, blood loss was lower (mean, 305.1 vs. 561.2 ml, P < .001) and hospital stay was shorter (mean, 8.2 vs. 15.4 days, P < .001) in the minimally invasive surgery group. Using multivariate analysis, lymphovascular space invasion was identified as poor prognostic factor for progression-free survival (adjusted hazard ratio [HR], 3.054; 95 % confidence interval [CI], 1.521-6.132; P = .002) and overall survival (adjusted HR, 3.918; 95 % CI, 1.455-10.551; P = .007), whereas age ≥ 60 years was poor prognostic factor for only overall survival (adjusted HR, 5.0953; 95 % CI, 1.660-15.378; P = .004). CONCLUSIONS: Surgical outcomes did not differ between the minimally invasive and open surgery group in patients with non-endometrioid endometrial cancer. Lymphovascular space invasion was a significant survival factor in this context.

Exploring metastasis and recurrence patterns in low-risk grade 3 endometrial cancer: A multicenter retrospective cohort study.

OBJECTIVE: Females with low-risk endometrial cancer typically have low lymph node metastasis risk and promising prognosis without lymphadenectomy. However, the impact of grade 3 endometrial cancer on nodal involvement, recurrence, and prognosis within this specific subgroup remains unclear. Therefore, in this study, we aimed to investigate the prognosis, patterns of metastasis, and recurrence in a subgroup of females with grade 3 early-stage low-risk endometrioid endometrial cancer. METHODS: We identified patients from the endometrial cancer cohorts of seven institutional hospitals. The study included patients who underwent hysterectomy between January 2013 and December 2021 with preoperative endometrioid histological type, less than half myometrial invasion, no tumor spread outside the corpus on imaging, normal CA-125 level, and histological grade 3. The clinicopathological characteristics and survival outcomes of the patients were collected. Recurrence-free survival was estimated using the Kaplan-Meier method and compared using the log rank test. RESULTS: Overall, 36 patients were included in this analysis. Of the 33 patients who underwent lymphadenectomy, 1 (1/33, 3.0 %) had lymph node metastasis and 27 (75.0 %) received adjuvant therapy. At a median follow-up of 58 months, three females (8 %) had recurrence and all cases involved lymph nodes. The 5-year recurrence-free survival was 88.7 %. No significant difference was observed in the recurrence-free survival between females who did and did not undergo lymphadenectomy (p = 0.554). CONCLUSION: Females diagnosed with low-risk grade 3 endometrial cancer typically have favorable prognosis. However, lymph node metastasis and recurrence risks still exist, with all recorded instances of recurrence involving lymph nodes.

Update on the oncologic and obstetric outcomes of medroxyprogesterone acetate treatment for atypical endometrial hyperplasia and endometrial cancer.

AIMS: To evaluate the safety and effectiveness of high-dose oral medroxyprogesterone acetate (MPA) therapy as a fertility-sparing treatment for patients diagnosed with atypical endometrial hyperplasia (AEH) and endometrioid carcinoma G1 without myometrial invasion (G1EC). Particular attention was given to the extended administration and readministration of MPA for patients with persistent disease following initial treatment and those with recurrence. METHODS: We conducted a retrospective analysis of data from 79 patients who underwent daily oral MPA treatment between 2005 and 2024 at Nagoya University Hospital. Patient characteristics, treatment outcomes, factors contributing to recurrence, and post-MPA therapy pregnancies were examined. RESULTS: MPA therapy achieved a remarkable complete response (CR) rate of 91.1%. The median time to achieve CR was 26.0 and 40.0 weeks for AEH and G1EC patients, respectively. Importantly, 27 patients (39.7%) attained CR after more than 6 months of treatment, including 8 patients (11.8%) who achieved CR after more than a year of treatment. The recurrence rates were 52.9% for AEH and 64.7% for G1EC. Twenty eight patients resumed MPA treatment, and 23 achieved second CR. Notably, recurrence was not associated with clinical factors such as age, body mass index, or post-CR pregnancy. Among patients who attempted pregnancy after achieving CR, 22 live births were successfully achieved. CONCLUSIONS: High-dose oral MPA therapy demonstrated both safety and efficacy for preserving fertility in patients with AEH and G1EC, resulting in a high CR rate. MPA extension and readministration proved to be beneficial strategies for managing patients with recurrence and persistent disease following initial treatment.

Genetic association of lipids and lipid-lowering drug target genes with Endometrial carcinoma: a drug target Mendelian randomization study.

Background: Aberrant lipid metabolism is intricately linked to the development of endometrial cancer, and statin lipid-lowering medications are regarded as promising adjunctive therapies for future management of this malignancy. This study employed Mendelian randomization (MR) to explore the causal association between lipid traits and endometrial cancer while assessing the potential impact of drug targets on lower lipids on endometrial cancer. Method: Two-sample Mendelian randomization was employed to probe the causal association between lipid traits and endometrial carcinoma. Drug-target Mendelian randomization was also utilized to identify potential drug-target genes for managing endometrial carcinoma. In instances where lipid-mediated effects through particular drug targets were notable, the impacts of these drug targets on endometrial carcinoma risk factors were investigated to bolster the findings. Result: No causal association between genetically predicted lipid traits (LDL-C, TG, TC, and HDL-C) and EC was found in two-sample Mendelian randomization. In drug target Mendelian randomization, genetic modeling of apolipoprotein B (APOB) (OR [95%CI]=0.31, [0.16-0.60]; p=4.73e-04) and cholesteryl ester transfer protein (CETP) (OR [95%CI]=1.83, [1.38-2.43]; p=2.91e-05) genetic mimicry was associated with non-endometrioid carcinoma. Conclusion: The results of our MR study revealed no causal association between genetically predicted lipid traits (LDL-C, TG, TC, and HDL-C) and EC. Among the six lipid-lowering drug targets, we observed a significant association between lower predicted APOB levels and higher CETP levels with an increased risk of endometrioid carcinoma. These findings provide novel insights into the importance of lipid regulation in individuals with endometrial carcinoma, warranting further clinical validation and mechanistic investigations.

Mesothelin promotes the migration of endometrioid carcinoma and is associated with the MELF pattern.

Mesothelin (MSLN) is expressed in the mesothelium in normal tissues but is overexpressed in various malignant tumors. In this study, we searched for genes that were more frequently expressed in cases of endometrioid carcinoma (EC) with the MELF (microcystic, elongated, and fragmented) pattern using laser microdissection and RNA sequencing, and found that MSLN was predominantly expressed in cases with the MELF pattern. The role of MSLN in EC was analyzed by generating MSLN-knockout and -knockdown EC cell lines. MSLN promoted migration and epithelial-mesenchymal transition (EMT). Moreover, we found that cadherin-6 (CDH6) expression was regulated by MSLN. MSLN is known to bind to cancer antigen 125 (CA125), and we found that CA125 can regulate CDH6 expression via MSLN. Immunohistochemical investigations showed that MSLN, CA125, and CDH6 expression levels were considerably elevated in EC with the MELF pattern. The expression of CA125 was similar to that of MSLN not only in terms of immunohistochemical staining intensity but also the blood level of CA125. Our results showed that MSLN contributes to the migration and EMT of EC cells through upstream CA125 and downstream CDH6. Therefore, MSLN has potential as a therapeutic target for EC with the MELF pattern.

Basket study of oral progesterone antagonist onapristone extended release in progesterone receptor-positive recurrent granulosa cell, low-grade serous ovarian cancer, or endometrioid endometrial cancer.

OBJECTIVE: To determine the safety and efficacy of the oral progesterone antagonist onapristone extended release (onapristone-XR) in patients with recurrent progesterone receptor (PR)-positive adult-type granulosa cell tumor (aGCT), low-grade serous ovarian cancer (LGSOC), or endometrioid endometrial cancer (EEC). METHODS: This single-institution phase II study included patients with PR-positive aGCT, LGSOC, or EEC who received ≥1 prior line of chemotherapy. Patients were enrolled from 5/2019-5/2020. PR status was evaluated via immunohistochemistry. Eligible patients had PR expression ≥1% on tissue collected within 3 years of enrollment. Patients received 50 mg of onapristone-XR twice daily until disease progression or treatment discontinuation. Adverse events were graded by Common Terminology Criteria for Adverse Events version 5.0. The primary endpoint was overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors 1.1. Secondary endpoints were response duration, clinical benefit rate (CBR), and safety. RESULTS: Five patients with LGSOC and 1 with EEC enrolled, but both cohorts closed early due to slow accrual. Fourteen patients with aGCT enrolled and completed stage 1 accrual. No responses were observed. Four patients with LGSOC were evaluable, with median PFS of 4.4 months (range, 1.8-NE) and CBR of 50% (range, 6.8%-93.2%). All 14 patients with aGCT were evaluable, with median PFS of 2.8 months (range, 1.6-4.9), 6-month PFS rate of 21.4% (range, 5.2%-44.8%), 12-month PFS rate of 14.3% (range, 2.3%-36.6%), and a CBR of 35.7% (range, 12.8%-64.9%). CONCLUSIONS: The study did not meet its primary endpoint. While onapristone-XR was well tolerated in all 3 arms, no objective responses were observed.

Corded and Hyalinized Endometrioid Endometrial Carcinoma: A Rare Case Treated With Robot-Assisted Surgery.

Endometrial carcinoma is the sixth most common cancer among women worldwide. Minimally invasive surgery (MIS) has become the preferred treatment, offering similar survival outcomes to laparotomy with lower complication rates. Corded and hyalinized endometrioid carcinoma (CHEC) is a rare and diagnostically challenging variant of endometrioid carcinoma, first described in 2005, characterized by a biphasic appearance of traditional low-grade endometrioid adenocarcinoma and corded and spindled cells embedded in a hyaline stroma. A 55-year-old nulligravid woman presented with abnormal genital bleeding for 10 days. Initial evaluations, including transvaginal ultrasonography and histological examination, confirmed adenocarcinoma. Imaging studies (magnetic resonance imaging [MRI] and computed tomography [CT]) revealed a thickened endometrium (11 mm) with no myometrial invasion, enlarged pelvic lymph nodes, or distant metastasis. Tumor markers were within normal ranges. She underwent robot-assisted laparoscopic total hysterectomy, bilateral adnexectomy, and pelvic lymph node biopsy using the da Vinci Xi system (Intuitive Surgical, Sunnyvale, CA). Histopathological examination revealed CHEC, with characteristic epithelioid and spindled cells arranged in cords within a hyalinized stroma. Immunohistochemical staining showed focal positivity for cytokeratin AE1/AE3, weak estrogen receptor positivity, and nuclear ß-catenin expression, distinguishing it from carcinosarcoma. The diagnosis was confirmed as CHEC, FIGO 2008 stage IA (pT1aN0M0). The patient remained disease-free 18 months post-surgery. CHEC is a rare variant of endometrioid carcinoma with unique histological features. It typically presents in younger patients at an early stage and has a favorable prognosis. Accurate diagnosis is crucial to differentiate it from more aggressive tumors like carcinosarcoma, preventing overtreatment. The immunohistochemical profile, particularly nuclear ß-catenin accumulation, is useful in distinguishing CHEC from carcinosarcoma. This is the first documented case of CHEC successfully treated with robot-assisted surgery. Increased awareness among pathologists and clinicians is essential for accurate diagnosis and optimal management of this rare tumor variant.

Niraparib Maintenance Therapy for Brain Metastasis in Ovarian Endometrioid Adenocarcinoma With Peritoneal Carcinomatosis: A Comprehensive Case Study and Literature Review.

Brain metastasis is a rare complication of ovarian cancer, always found at the advanced stage. Even though different multimodal approaches are available, including surgical intervention and radiotherapy, there are no official guidelines for handling this serious complication. Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors are a group of medications initially used for maintenance therapy in platinum-sensitive recurrent ovarian cancer. Niraparib has shown some efficacy in patients with brain metastasis due to its unique properties of penetrating the blood-brain barrier. Here, we present the case of a 51-year-old patient with advanced ovarian cancer with no germline breast cancer susceptibility gene (BRCA) mutations. Despite undergoing surgery and multiple rounds of chemotherapy, the patient's condition worsened, culminating in brain metastasis. Given her neurological issues, radiotherapy was not an option, prompting the initiation of a 300 mg dose of niraparib. To date, only sporadic case reports in the literature have described patients with ovarian cancer treated with niraparib and complicated by brain metastasis. Our case is unique because it is the first case of a patient with the endometrioid type of ovarian cancer.

Retained PAX2 expression associated with DNA mismatch repair deficiency in endometrial endometrioid adenocarcinoma.

AIMS: Loss of expression of tumour suppressor PAX2 and MMR deficiency (dMMR) has been frequently seen in endometrial endometrioid adenocarcinoma (EEC). However, the relationship between PAX2 expression and MMR status is unknown. METHODS AND RESULTS: We studied the PAX2 expression and examined its association with MMR status at the protein and genetic levels in 180 cases of EEC. Overall, total loss of PAX2 expression was found in about 70%, while retained PAX2 expression was seen in 30% of EEC. Among 125 cases with loss of PAX2, 68.8% were found in EECs with pMMR, while 31.2% were seen in those with dMMR. Among 55 cases of EECs with retained PAX2 expression, 92.7% were EECs with dMMR and 7.3% were those with pMMR (P < 0.001). While dMMR cases with MLH1 hypermethylation show almost equal retained or loss of PAX2 expression (52% versus 48%), dMMR with genetic alterations had significantly more retained PAX2 expression than loss of PAX2 (92.3% versus 7.7%), regardless of somatic or germline mutations. Loss of PAX2 was observed in 97.3% of dMMR with MLH1 hypermethylation compared to 2.7% of dMMR with genetic alterations (P < 0.001). Aggressive features such as higher tumour grades (FIGO 2-3) and advanced clinical stage (T2-T4) were significantly more frequently seen in dMMR with retained PAX2 expression, compared those to pMMR with loss of PAX2 expression. CONCLUSION: Our study demonstrates a close correlation between retained PAX2 expression and dMMR in EEC. The molecular mechanism and clinical significance linking these two pathways in EEC remains to be unravelled.

Blood Vessel Invasion Is an Independent Prognostic Factor in Endometrial Endometrioid Carcinoma Compared to Lymph Vessel Invasion and Myometrial Invasion Pattern.

We studied 115 cases of EEC diagnosed on hysterectomy specimens. Double immunohistochemical staining (D2-40/CD31) was performed in all 115 cases to show LVI and BVI on the same slide. MELF pattern invasion was present in 24/115 (21%) cases. MELF-positive tumors had a higher frequency of LVI than MELF-negative tumors (58% and 23%, respectively); the frequency of BVI was twice as high in MELF-positive tumors in comparison to MELF-negative tumors (25% and 12%, respectively). These differences were significant (p ˂ 0.0001). All tumors with positive BVI also had a concomitant LVI. The presence of MELF invasion had no impact on overall survival, confirming previous studies. 5-year survival rates were almost equal in cases with negative LVSI and cases with positive isolated LVI (98% vs. 97%). However, in cases where BVI was also present, the 5-year survival rate was significantly lower, 63% (p ˂ 0.0001). Furthermore, BVI proved to be an independent prognostic factor for overall survival, disease-free survival, and recurrence in the multivariate analysis. In conclusion, MELF pattern invasion is a good predictor of lymphatic and blood vessel invasion but has no prognostic value. Our results suggest that BVI in EEC has greater clinical value than isolated LVI or myometrial invasion patterns, and the therapeutic approach should be guided by BVI presence. Therefore, we hope this study will promote the routine evaluation of BVI in the context of EEC diagnostic procedures.

Promoter methylation status of RASSF1A and RASSF2A tumor suppressor genes in endometrial endometrioid carcinomas.

We aimed to investigate the promoter methylation status of RASSF1A and RASSF2A tumor suppressor genes in endometrial endometrioid carcinomas with p53 wild type and mismatch repair proficient. Genomic DNAs were isolated from 50 specimens (15 formalin-fixed paraffin embedded tumor tissues, 15 paired blood samples and 20 normal endometrial tissues). Bisulfide modification and methylation-specific polymerase chain reaction were performed. As a result of the study, while no significance was found for RASSF1A gene (p = 0.08), a statistically significance was found for RASSF2A gene (p < 0.001), RASSF2A gene methylation status was also found higher in high grade tumors, advanced age (≥50) and nonsmokers groups. Our results indicate that RASSF2A gene may play a role in the carcinogenesis of endometrioid and it could be potential biomarker for early detection for endometrioid carcinoma. Further and larger investigations are needed to confirm our results.

Molecular classification of metastatic and recurrent endometrial endometrioid carcinoma: prognostic relevance among low- and high-stage tumours.

AIMS: Molecular classification according to The Cancer Genome Atlas (TCGA) improves endometrial endometrioid carcinoma (EEC) prognostication and has specific treatment implications; however, original data were skewed towards low-grade and low-stage tumours. Herein, we molecularly classify EECs metastatic at the time of diagnosis or with subsequently documented recurrent/metastatic disease to examine correlation with clinical outcomes. METHODS: TCGA categories include POLE-mutated, microsatellite instability (MSI), p53 abnormal (p53 abnl) and no specific molecular profile (NSMP). POLE targeted sequencing at exons 9, 11, 13 and 14 and immunohistochemistry (IHC) for PMS2, MSH6 and p53 were performed to establish molecular classification. RESULTS: The distribution in our cohort of 141 EECs was similar to that generally reported in EEC, with nine POLE-mutated (6%), 45 MSI (32%), 16 p53 abnl (11%) and 71 NSMP (50%), with similar distributions between low- and high-stage cohorts. We demonstrate that when stratified by molecular subtype, disease-specific survival from the time of high-stage (stages III-IV) presentation or time of recurrence in low-stage (stages I-II) disease among metastatic and/or recurrent EEC is strongly associated with TCGA classification (high-stage P = 0.02, low-stage P = 0.017). Discordant molecular classification between primary and metastatic/recurrent tumours occurred in four of 105 (3.8%) patients, two related to PMS2/MSH6 IHC and two related to p53 IHC. CONCLUSIONS: We demonstrate that molecular classification is prognostically relevant not only at the time of diagnosis, but also at the time of recurrence and in the metastatic setting. Rare subclonal alterations occur and suggest a role for confirming TCGA classification in recurrent/metastatic tumours.

Clinicopathological characteristics and fertility preserving treatment of atypical polypoid adenomyoma.

Objective: Atypical polypoid adenomyoma (APA) is a rare benign tumor frequently diagnosed in young women that may coexist with or progress to atypical endometrial hyperplasia (EAH) or endometrioid endometrial carcinoma (EEC). This study aimed to investigate which subset of patients with APA are prone to concurrent or subsequent EAH or EEC, evaluate the necessity of progestin treatment in patients with APA only after achieving a complete response (CR) through hysteroscopic lesion resection, and assess the impact of concurrent APA on the fertility-preserving treatment of EAH or EEC. Methods: This retrospective single-center study analyzed 86 patients with APA treated at the Obstetrics and Gynecology Hospital of Fudan University between January 2010 and October 2021. Patients with EAH or EEC only who underwent fertility-preserving treatment during the same period were matched in a 2:1 ratio with patients with concurrent APA and EAH or EEC. The clinicopathological characteristics, treatments, and prognosis were analyzed. Results: The median patient age was 31 years (range 21-47 years). Among the 86 included patients, nine underwent total hysterectomy, 62 received conservative treatment, and the remaining 15 were lost to follow-up. A comparison of the 16 patients with APA only versus the 58 patients with APA and concurrent or subsequent EAH or EEC revealed that a homeostasis model assessment of insulin resistance (HOMA-IR) of > 2.2 (P = 0.047) and high-density lipoprotein (HDL) concentration of < 1.2 mmol/L (P = 0.028) were independent risk factors for EAH or EEC in patients with APA. Among the 17 patients with APA only who received conservative treatment and achieved a CR after hysteroscopic lesion resection, 13 received hormone treatment for a median duration of 6.3 months. The median follow-up time for these 17 patients was 49.0 months, during which no recurrence of APA was observed, but six patients developed endometrial hyperplastic diseases. Regarding the impact of concurrent APA on fertility-preserving treatment for EAH or EEC, the median time to achieve a CR was 24.0 weeks (95% confidence interval [CI]: 23.0-40.4) in the APA group and 26.0 weeks (95% CI: 24.3-32.3) in the non-APA group (P = 0.424). There were no significant differences between the two groups in the outcomes of fertility-preserving treatment. Conclusion: Patients with APA only may still develop endometrial hyperplastic diseases after complete resection of the lesion under hysteroscopy to achieve a CR, particularly those with a HOMA-IR of > 2.2 or HDL concentration of < 1.2 mmol/L. Concurrent APA did not affect the efficacy of fertility-preserving treatment in patients with EAH or EEC.

Endometrioid ovarian carcinoma landscape: pathological and molecular characterization.

Endometrioid ovarian cancers (EOvC) are usually managed as serous tumors. In this study, we conducted a comprehensive molecular investigation to uncover the distinct biological characteristics of EOvC. This retrospective multicenter study involved patients from three European centers. We collected clinical data and formalin-fixed paraffin-embedded (FFPE) samples for analysis at the DNA level using panel-based next-generation sequencing and array-comparative genomic hybridization. Additionally, we examined mRNA expression using NanoString nCounter® and protein expression through tissue microarray. We compared EOvC with other ovarian subtypes and uterine endometrioid tumors. Furthermore, we assessed the impact of molecular alterations on patient outcomes, including progression-free survival (PFS) and overall survival (OS). Preliminary analysis of clinical data from 668 patients, including 86 (12.9%) EOvC, revealed more favorable prognosis for EOvC compared with serous ovarian carcinoma (5-year OS of 60% versus 45%; P = 0.001) driven by diagnosis at an earlier stage. Immunohistochemistry and copy number alteration (CNA) profiles of 43 cases with clinical data and FFPE samples available indicated that EOvC protein expression and CNA profiles were more similar to endometrioid endometrial tumors than to serous ovarian carcinomas. EOvC exhibited specific alterations, such as lower rates of PTEN loss, mutations in DNA repair genes, and P53 abnormalities. Survival analysis showed that patients with tumors harboring loss of PTEN expression had worse outcomes (median PFS 19.6 months vs. not reached; P = 0.034). Gene expression profile analysis confirmed that EOvC differed from serous tumors. However, comparison to other rare subtypes of ovarian cancer suggested that the EOvC transcriptomic profile was close to that of ovarian clear cell carcinoma. Downregulation of genes involved in the PI3K pathway and DNA methylation was observed in EOvC. In conclusion, EOvC represents a distinct biological entity and should be regarded as such in the development of specific clinical approaches.

Endometrioid carcinoma of the fallopian tube misdiagnosed as an infected endometrioma: A case report.

INTRODUCTION: Fallopian tube cancer is a rare tumor, representing between 0.3 and 1.8 % of all malignant tumors in the gynecological sphere. Due to the proximity of the uterus and ovary, the diagnosis of primary fallopian tube cancer is very difficult to establish and relies on very strict criteria. The endometrioid form is exceptional and of controversial etiopathogenesis. Only a few cases have been previously reported. Diagnosis most often occurs incidentally during histological examination. This case presents a distinctive aspect with the rare occurrence of endometrioid-type fallopian tube cancer, notably associated with endometriosis, and initially misdiagnosed as an infected endometrioma. It underscores the diagnostic complexities encountered in identifying primary fallopian tube cancer. CASE REPORT: We present the case of a 49-year-old patient, followed for chronic pelvic pain associated with menorrhagia. Imaging revealed a myomatous and adenomyotic uterus, a right ovarian endometrioma, and a left multicystic ovarian formation with thick walls, measuring 135 mm, requiring histological verification. She underwent an exploratory laparotomy. During the procedure, extensive retro- and supravaginal adhesive tissue involving the uterus, both adnexa, and the digestive tract was found. Careful adhesiolysis was performed. The left adnexa harbored a formation suggestive of an infected endometrioma. A total hysterectomy with bilateral adnexectomy and peritoneal washing was performed. The postoperative course was uneventful. Histopathological examination revealed an endometrioid carcinoma of the left fallopian tube, classified as pT1a according to FIGO guidelines. DISCUSSION: Tubal cancer is a rare cancer of unknown etiology, underestimated, and sometimes confused with ovarian pathology. Preoperative diagnosis is difficult because the clinical presentation is polymorphic and imaging is nonspecific. The endometrioid form is exceptional and of controversial etiopathogenesis. Treatment mirrors that of malignant epithelial ovarian tumors, with prognosis depending on FIGO stage and histological type. CONCLUSION: Due to its unpredictable nature, fallopian tube cancer should not be overlooked as a differential diagnosis for any adnexal mass.

Label-free imaging diagnosis and collagen-optical evaluation of endometrioid adenocarcinoma with multiphoton microscopy.

The assessment of tumor grade and pathological stage plays a pivotal role in determining the treatment strategy and predicting the prognosis of endometrial cancer. In this study, we employed multiphoton microscopy (MPM) to establish distinctive optical pathological signatures specific to endometrioid adenocarcinoma (EAC), while also assessing the diagnostic sensitivity, specificity, and accuracy of MPM for this particular malignancy. The MPM technique exhibits robust capability in discriminating between benign hyperplasia and various grades of cancer tissue, with statistically significant differences observed in nucleocytoplasmic ratio and second harmonic generation/two-photon excited fluorescence intensity. Moreover, by utilizing semi-automated image analysis, we identified notable disparities in six collagen signatures between benign and malignant endometrial stroma. Our study demonstrates that MPM can differentiate between benign endometrial hyperplasia and EAC without labels, while also quantitatively assessing changes in the tumor microenvironment by analyzing collagen signatures in the endometrial stromal tissue.