Primary extra-uterine and extra-ovarian mullerian adenosarcoma: case report and literature review.

BACKGROUND: Extra-uterine mullerian adenosarcomas have varying biological behaviours depending on the presence of endometriosis or sarcomatous overgrowth. These behaviours manifest according to the tumours' histological characteristics and sites of origin. The best treatment and oncologic outcome have not been clarified because only a few cases of extra-uterine and extra-ovarian adenosarcoma have been described in the literature. Here, we report a case of primary peritoneal adenosarcoma with sarcomatous overgrowth and review all reported cases of adenosarcomas arising outside of the uterus and outside the ovaries to identify the best treatment options and clarify outcomes. CASE PRESENTATION: A 79-year-old woman was referred to our Department with an abdominal mass resembling a fibroid with a haemorrhage. Her gynaecological history was negative. A transvaginal and transabdominal ultrasound examination revealed a multicystic mass resembling an ovarian tumour arising from the pelvis and extending up to the abdomen. At laparotomy a peritoneal mass arising from Douglas peritoneum was resected. The uterus and adnexa appeared normal, and a supra-cervical hysterectomy with bilateral salpingo-oophorectomy was performed. No macroscopic residual disease was present. Final pathology diagnosed a malignant peripheral nerve sheath tumors with divergent differentiation. Four weeks later a new, multicystic mass was found. Due to the progressive poor condition, the patient died four months after diagnosis. Histological slides were reviewed by external expert pathologists and the final diagnosis was of extra-genital adenosarcoma with sarcomatous overgrowth. Furthermore, we also collected and analysed articles written in English regarding extra-uterine and extra-ovarian adenosarcomas published between January 1974 and October 2016. PubMed was used as a database for this search. Clinical and pathological characteristics, treatments and outcomes were assessed. CONCLUSIONS: Only 41 cases has been reported in literature. Previous endometriosis and sarcomatous overgrowth showed an inverse effect on prognosis. Endometriosis was confirmed to have a positive effect on disease free survival Complete surgical resection is the mainstay of treatment. A worldwide registry is urgently required to collect data to standardize treatment and to obtain reliable data on prognosis.

Impact of the Food and Drug Administration Safety Communication on the Use of Power Morcellator in Daily Clinical Practice: An Italian Survey.

STUDY OBJECTIVE: To assess the impact of the Food and Drug Administration (FDA) warning about power morcellation use on the daily clinical practice of Italian gynecologists. DESIGN: Electronic survey mailed to the main gynecologic centers (Canadian Task Force Classification type III). SETTING: Unit of Obstetrics and Gynecology, IRCCS - Arcispedale S. Maria Nuova di Reggio Emilia (Italy). PATIENTS: The study did not include patient data. INTERVENTION: There was no intervention. MEASUREMENTS AND MAIN RESULTS: From 490 surveys sent out, 426 replies were included in the final analysis (return rate = 86.9%). Four hundred of the 426 (93.9%) gynecologists were aware of the FDA warning. One hundred fifty of 302 (49.7%) of experienced gynecologists and 176 of 349 (50.4%) of oncology gynecologists considered laparoscopy the best approach for myomectomy. The FDA communication was considered overly restrictive by experienced and oncology gynecologists who declared that they had no intention of changing their surgical approach. Two hundred fifty of the 426 (58.7%) gynecologists declared that they would change their surgical approach only to prevent legal litigation. CONCLUSION: The FDA warning also affected Italian gynecologists. Particularly, less experienced gynecologists and those without oncologic practice seem to be more interested in avoiding legal litigation rather than a real clinical risk of upstaging an unexpected leiomyosarcoma. Fear of undiagnosed sarcoma could increase the number of laparotomies.

Polymorphisms in cyclooxygenase-2 gene in endometrial cancer patients.

The enzyme cyclooxygenase 2 is an inducible enzyme expressed at sites of inflammation and in a variety of malignant solid tumors such as endometrial cancer (EC). In EC patients, its over-expression is correlated with progressive disease and poor prognosis. The expression is encoded by a polymorphic gene, called PTGS2. The aim of the current study was to test the hypothesis that rs5275 polymorphism of PTGS2 influence the prognosis of EC patients. This paper is a retrospective cohort study. Clinical and pathological data were extrapolated and genotypes were assessed on formalin-fixed and paraffin-embedded non-tumor tissues. A total of 159 type I EC patients were included in the final analysis. Univariate analysis indicated that patients with rs5275 genotype CC have a lower risk to develop a grade (G) 2-3 endometrial cancer. rs5275 effect on EC grading was confirmed by multivariate analysis also after data adjusting for age, BMI, parity, hypertension, and diabetes. Adjusted odds ratio (OR) confirmed that patients with rs5275 genotype CC have a risk 80 % lower (OR = 0.20, P = 0.009) to develop a G2 and/or G3 EC in comparison with patients with TT or TC genotype. Differentiation of the type 1 EC is significantly and independently influenced by rs5275 polymorphism. rs5275 CC patients have a lower risk to present a G2-G3 EC.

HNF1B polymorphism influences the prognosis of endometrial cancer patients: a cohort study.

BACKGROUND: HNF1B (formerly known as TCF2) gene encodes for a transcription factor that regulates gene expression involved in normal mesodermal and endodermal developments. A close association between rs4430796 polymorphism of HNF1B gene and decreased endometrial cancer (EC) risk has been demonstrated. The aim of the current study was to test the hypothesis that rs4430796 polymorphism can influence the prognosis of EC patients. METHODS: Retrospective cohort study. Clinical and pathological data were extrapolated and genotypes were assessed on formalin-fixed and paraffin-embedded non-tumour tissues. The influence of patients' genotype on overall survival and progression free survival were our main outcome measures. RESULTS: A total of 191 EC patients were included in the final analysis. Overall survival differed significantly (P = 0.003) among genotypes. At multivariate analysis, a significant (P < 0.05) effect on overall survival was detected for FIGO stage, and rs4430796 polymorphism of HNF1B gene. After grouping EC patients according to adjuvant treatment, rs4430796 polymorphism resulted significantly (P < 0.001) related to overall survival only in subjects who received radiotherapy plus chemotherapy. A significant (P = 0.014) interaction between rs4430796 polymorphism and chemo-radiotherapy was also detected. Finally, only a trend (P = 0.090) towards significance was observed for rs4430796 polymorphism effect on progression free survival. CONCLUSIONS: rs4430796 polymorphism of HNF1B gene influences independently the prognosis of EC patients with a potential effect on tumor chemo-sensitivity.

Coxalgia? Call the gynecologist.

Cellular angiofibroma is a rare mesenchymal tumor that usually affects the vulvar region. It is commonly asymptomatic and treated with radical excision. We describe the first case of cellular angiofibroma located in the retroperitoneum presenting with coxalgia and laparoscopically treated. At the 6-month follow-up, the patient was coxalgia and disease free. Coxalgia is an unusual symptom for gynecologists; nevertheless, it is possible that several neoplasms may originate in the female pelvis, so any symptom requires careful evaluation. The laparoscopic approach may be effective in removing cellular angiofibroma, avoiding injuries to surrounding structures and unesthetic scarring and leading to a faster recovery.

Conversion in endometrial cancer patients scheduled for laparoscopic staging: a large multicenter analysis: conversions and endometrial cancer.

BACKGROUND: Data on patients with endometrial cancer converted to laparotomy are totally lacking. The aim of the present study was to evaluate surgical and oncological outcomes in patients with endometrial cancer scheduled for laparoscopic staging but converted to laparotomy. METHODS: Data of consecutive patients who had undergone surgery for staging endometrial cancer in seven Italian centers were reviewed. Patients' characteristics and surgical and oncological data were noted and analyzed according to surgery, i.e. laparotomy, laparoscopy, and laparoscopy converted to laparotomy. RESULTS: Seventy-one out of 512 (13.9 %) patients scheduled to laparoscopy were converted to laparotomy for reasons related to anesthesiology [38/71 (53.5 %)] or surgery [33/71 (46.5 %)]. The conversion rate varied among stages [41/460 (8.9 %), 13/27 (48.1 %), 17/25 (68.0 %) in patients with stage I, II, and endometrial cancers, respectively]. Significant (P < 0.05) differences among groups were detected in patients' age, body mass index and previous pelvic surgery, and in the distribution of stages and histotype of endometrial cancers. The Kaplan-Meier procedure showed that the cumulative probability of first recurrence (P = 0.089, 0.590 and 0.084 for stage I, II and III, respectively) and of death (P = 0.108, 0.567 and 0.372 for stage I, II and III, respectively) categorized by stages did not attain statistical significance by log-rank testing after correction for confounding factors. CONCLUSIONS: The surgical and oncological outcomes of converted patients are no different from those of patients staged successfully with laparoscopy or with laparotomy. The conversion to laparotomy should be not considered per se a complication.

Primary tuberculosis of the uterine cervix: keep it in mind.

INTRODUCTION: Primary tuberculosis of the cervix is extremely rare, with only 20 cases reported in the English literature since 1949. Here we report the 21st case--an Italian woman with no risk factors. CASE: A 50-year-old Italian nulliparous woman was referred to our gynecology unit for vaginal discharge. Her past history was negative. Colposcopy revealed an ulcerated lesion raising the suspicion of cervical cancer. A biopsy revealed a tuberculosis granuloma, and acid-fast bacillus was identified with Ziehl-Neelsen stain. As no other site of tuberculosis was found, primary cervical tuberculosis was diagnosed. CONCLUSIONS: Although rare in industrialized countries, cervical tuberculosis may affect even women without risk factors. It should thus be taken into account in the differential diagnosis of cervical cancer.

Primary neuroendocrine neoplasms of the vulva: A review of the MITO rare cancer group.

Gynecological neuroendocrine neoplasms are rare entities and can be divided into two groups: carcinoids and neuroendocrine carcinomas. Due to their rarity their management is not standardized. The aim of this work is to summarize and discuss the current literature evidence on this pathology. A scoping literature review was performed in multiple databases. Thirty-one studies were included: 30 case reports and one case series. Patients' age ranged between 28 and 92 years. Surgery was the most used treatment and the surgical approach included local excision (N = 16/31; 51.6%) with (N = 5/16; 31.25%) or without (N = 11/16; 68.75%) inguinal lymphadenectomy. Adjuvant radiotherapy was delivered in 12 (38.7%) cases; instead, platinum-based therapies were frequently used when chemotherapy was chosen for adjuvant treatment. The overall survival ranged between 20 days to 4 years. However, further research is needed; currently, multimodal approach including surgery, chemotherapy and radiotherapy appeared safe and feasible for the treatment of these rare and aggressive diseases.

A multicentric trial (Olympia-MITO 13) on the accuracy of laparoscopy to assess peritoneal spread in ovarian cancer.

OBJECTIVE: The objective of the study was to prospectively evaluate the accuracy of laparoscopy performed in satellite centers (SCs) to describe intraabdominal diffusion of advanced ovarian cancer (AOC). STUDY DESIGN: Patients with a clinical/radiological suspicion of AOC were included in the protocol. SCs were selected among those surgeons, spending a short intensive training period at the coordinator center (CC) to learn the application of staging laparoscopy (S-LPS) in AOC. All women underwent S-LPS at the SCs, and the surgical procedure was recorded and blindly reviewed at the CC. Calculating specificity, positive and negative predictive values, and the accuracy for each parameter with respect to the CC assessed the diagnostic performance of S-LPS. The Cohen's kappa was used to test the interobserver agreement of each parameter. RESULTS: One hundred sixty-eight cases were considered eligible for the study. A per-protocol analysis was performed on 120 cases. The worst laparoscopic assessable feature was mesenteric retraction, whereas the remaining variables ranged from 99.2% (peritoneal carcinomatosis) to 90% (bowel infiltration). All but 1 SC (SC number 4) reached an accuracy rate of 80% or greater for both single parameters and overall score. The Cohen's kappa and the P value for overall predicitive index value were 0.685 and .01, respectively, but improved to 0.773 and .388 after removing the SC number 4 from the analysis. CONCLUSION: S-LPS allows an accurate and reliable assessment of intraperitoneal diffusion of disease in AOC patients in trained gynecological oncology centers.

Gonadotropin releasing hormone agonist and levonorgestrel-intrauterine device followed by in vitro fertilization program as management strategy for an infertile endometrial cancer patient: a case report.

BACKGROUND: A progressive delay in the age of first conception results in an increased frequency of endometrial cancer patients in reproductive age and desiring childbearing. CASE: A 38-year-old infertile woman with stage I endometrioid adenocarcinoma was treated with gonadotropin releasing hormone agonist (GnRHa) and levonorgestrel-releasing intrauterine device (LNG-IUD). After disease remission, she underwent a controlled ovarian stimulation for standard in vitro fertilization (IVF) program and had a pregnancy delivering a healthy male baby. Total laparoscopic hysterectomy with bilateral salpingo-oophorectomy was performed four months after delivery. The patient is free of disease after 3-year follow-up. CONCLUSION: GnRHa plus LNG-IUD followed by IVF program is a safe and effective fertility-sparing strategy to manage infertile patients with stage I endometrial cancer.

The role of minimally invasive surgery in epithelial ovarian cancer treatment: a narrative review.

Objectives: The aim of this narrative review is to summarize the available evidence on the use of minimal invasive surgery (MIS) in the management of epithelial ovarian cancer (EOC). Background: MIS is currently performed to stage and treat EOC at different stage of presentation. We will evaluate risks and benefits of minimally invasive surgery for early stage EOC treatment, then potential advantages provided by staging laparoscopy in identifying patients suitable for primary cytoreductive surgery (PDS) will be discussed. Finally we will investigate the growing role of MIS in the treatment of advanced EOC after neoadjuvant chemotherapy (NACT) and in the treatment of EOC recurrence. Methods: An electronic database search was performed on PubMed, Medline, and Google Scholar for relevant studies up to December 2022. Conclusion: LPS represents a feasible surgical procedure for the staging and treatment in early, advanced and EOC relapse in selected patients treated in high-volume oncological centers by surgeons with adequate experience in advanced surgical procedures. Despite the increasing use of MIS over the last few years, randomized clinical trials are still needed to prove its effectiveness.

Primary Ovarian Leiomyosarcoma Is a Very Rare Entity: A Narrative Review of the Literature.

BACKGROUND: Primary ovarian leiomyosarcoma is a very rare malignancy characterized by unclear management and poor survival. We reviewed all the cases of primary ovarian leiomyosarcoma to identify prognostic factors and the best treatment. METHODS: We collected and analyzed the articles published in the English literature regarding primary ovarian leiomyosarcoma from January 1951 to September 2022, using PubMed research. Clinical and pathological characteristics, different treatments and outcomes were analyzed. RESULTS: 113 cases of primary ovarian leiomyosarcoma were included. Most patients received surgical resection, associated with lymphadenectomy in 12.5% of cases. About 40% of patients received chemotherapy. Follow-up information was available for 100/113 (88.5%) patients. Stage and mitotic count were confirmed to affect survival, and lymphadenectomy and chemotherapy were associated with a better survival rate. A total of 43.4% of patients relapsed, and their mean disease-free survival was 12.5 months. CONCLUSIONS: Primary ovarian leiomyosarcomas are more common in women in their 50s (mean age 53 years). Most of them are at an early stage at presentation. Advanced stage and mitotic count showed a detrimental effect on survival. Surgical excision associated with lymphadenectomy and chemotherapy are associated with increased survival. An international registry could help collect clear and reliable data to standardize the diagnosis and treatment.

An Innovative Drug Repurposing Approach to Restrain Endometrial Cancer Metastatization.

BACKGROUND: Endometrial cancer (EC) is the most common gynecologic tumor and the world's fourth most common cancer in women. Most patients respond to first-line treatments and have a low risk of recurrence, but refractory patients, and those with metastatic cancer at diagnosis, remain with no treatment options. Drug repurposing aims to discover new clinical indications for existing drugs with known safety profiles. It provides ready-to-use new therapeutic options for highly aggressive tumors for which standard protocols are ineffective, such as high-risk EC. METHODS: Here, we aimed at defining new therapeutic opportunities for high-risk EC using an innovative and integrated computational drug repurposing approach. RESULTS: We compared gene-expression profiles, from publicly available databases, of metastatic and non-metastatic EC patients being metastatization the most severe feature of EC aggressiveness. A comprehensive analysis of transcriptomic data through a two-arm approach was applied to obtain a robust prediction of drug candidates. CONCLUSIONS: Some of the identified therapeutic agents are already successfully used in clinical practice to treat other types of tumors. This highlights the potential to repurpose them for EC and, therefore, the reliability of the proposed approach.

Clinical Review of Mucosal Melanoma: The 11-Year Experience of a Referral Center.

INTRODUCTION: Mucosal melanoma is a rare neoplasm. Late diagnosis is caused by occult anatomic sites and scarcity of symptoms. Novel biological therapies have now become available. Demographic, therapeutical and survival records on mucosal melanoma are scarce. OBJECTIVES: To provide an 11-year retrospective clinical review of real-world data on mucosal melanomas managed in a tertiary referral center in Italy. METHODS: We included patients with histopathological mucosal melanoma diagnoses from January 2011 to December 2021. Data were collected until the last known follow-up or death. Survival analysis was performed. RESULTS: Among 33 patients, we found 9 sinonasal, 13 anorectal and 11 urogenital mucosal melanomas (median age 82, females 66.7%). Eighteen cases (54.5%) presented with metastasis (p<0.05). In the urogenital subgroup, only 4 patients (36.4%) had metastasis at diagnosis, all in regional lymph nodes. Sinonasal melanomas were surgically managed with a debulking procedure (44.4%); every case of anorectal and urogenital melanomas underwent radical surgery (30.8% and 45.5%). Fifteen patients were treated with biological therapy (p<0.05). Radiation therapy was used in all melanomas of the sinonasal region (p<0.05). Overall survival was longer for urogenital melanomas (26 months). Univariate analysis showed an increased hazard ratio for death in patients with metastasis. A negative prognostic value of metastatic status was reported by the multivariate model, while administration of first-line immunotherapy demonstrated a protective role. CONCLUSIONS: At diagnosis, the absence of metastatic disease is the most relevant factor that influences the survival of mucosal melanomas. Moreover, the use of immunotherapy might prolong the survival of metastatic mucosal melanoma patients.

Optimizing Outcomes through a Multidisciplinary Team Approach in Endometrial Cancer.

This study aimed to assess the impact of a multidisciplinary team (MDT) approach on outcomes with endometrial cancer (EC) patients, utilizing 2013-2020 data from the Reggio Emilia Cancer Registry. Recurrence rate, treatments, and outcome indicators were compared between the MDT (319 cases) and non-MDT (324 cases) groups. Among 643 cases, 52.4% were over 65 years old, 98% had microscopic confirmation, and 73% were in stage I. Surgery was performed in 89%, with 41% receiving adjuvant therapies. Recurrence rates (10%) were similar between the two groups, but MDT patients who were older and predominantly in stage I exhibited 79% recurrence within one year (21% in the non-MDT group). Disease-free survival (DFS) showed no significant difference [HR 1.1; 95% CI 0.7-1.6], while differences in overall survival (OS) were notable [HR 1.5; 95% CI 1.0-2.4]. The 5-year OS rates were 87% and 79% in the MDT and non-MDT groups. Comparing the 2013-2015 to 2016-2020 study periods, a shift towards caring for older women, more advanced-stage patients, and those residing outside the metropolitan area, along with a greater number of relapsed cases (from 16% to 76%), were accounted for. These findings underscore the impact of an MDT on EC outcomes, highlighting the evolving patient demographics over time.

Do Exophytic and Endophytic Patterns in Borderline Ovarian Tumors Have Different Prognostic Implications? A Large Multicentric Experience.

Borderline ovarian tumor (BOT) accounts for 15-20% of all epithelial ovarian tumors. Concerns have arisen about the clinical and prognostic implications of BOT with exophytic growth patterns. We retrospectively reviewed all cases of BOT patients surgically treated from 2015 to 2020. Patients were divided into an endophytic pattern (with intracystic tumor growth and intact ovarian capsule) and an exophytic pattern (with tumor growth outside the ovarian capsule) group. Among the 254 patients recruited, 229 met the inclusion criteria, and of these, 169 (73.8%) belonged to the endophytic group. The endophytic group showed more commonly an early FIGO stage than the exophytic group (100.0% vs. 66.7%, p < 0.001). Furthermore, tumor cells in peritoneal washing (20.0% vs. 0.6%, p < 0.001), elevated Ca125 levels (51.7% vs. 31.4%, p = 0.003), peritoneal implants (0 vs. 18.3%, p < 0.001), and invasive peritoneal implants (0 vs. 5%, p = 0.003) were more frequently observed in the exophytic group. The survival analysis showed 15 (6.6%) total recurrences, 9 (5.3%) in the endophytic and 6 (10.0%) patients in the exophytic group (p = 0.213). At multivariable analysis, age (p = 0.001), FIGO stage (p = 0.002), fertility-sparing surgery (p = 0.001), invasive implants (p = 0.042), and tumor spillage (p = 0.031) appeared significantly associated with recurrence. Endophytic and exophytic patterns in borderline ovarian tumors show superimposable recurrence rates and disease-free survival.

Impact of 2 years of COVID-19 pandemic on ovarian cancer treatment in IRCCS-AUSL of Reggio Emilia.

OBJECTIVE: To assess compliance with the 2019 regional recommendation to centralize epithelial ovarian cancer (EOC) patients and to assess whether the COVID-19 pandemic has affected the quality of care for EOC patients. METHODS: We compared data from EOC patients treated before the introduction of the 2019 regional recommendation (2018-2019) with data obtained from EOC patients treated after the regional recommendation was adopted during the first 2 years of the COVID-19 pandemic (2020-2021). Data were retrieved from the Optimal Ovarian Cancer Pathway records. R software version 4.1.2 (the R Foundation for Statistical Computing, Vienna, Austria) was used for the statistical analysis. RESULTS: 251 EOC patients were centralized. The number of EOC patients centralized increased from 2% to 49% despite the COVID-19 pandemic. During the COVID-19 pandemic, there was an increase in the use of neoadjuvant chemotherapy and interval debulking surgery. There was an improvement in the percentage of Stage III patients without gross residual disease following both primary and interval debulking surgery. The percentage of EOC cases discussed by the multidisciplinary tumor board (MTB) increased from 66% to 89% of cases. CONCLUSION: Despite the COVID-19 pandemic, centralization has increased and the quality of care has been preserved thanks to the MTB.

Cerebellar metastasis of ovarian cancer: a case report.

BACKGROUND: Ovarian cancer is metastatic at presentation in about 62% of cases, but brain metastases are rare, reported in 3.3-4% of patients. Brain metastasis seems to be more frequent in advanced stages at diagnosis and in patients with BRCA1/2 mutation. CASE PRESENTATION: We present a case of a 47-year-old Caucasian woman, BRCA wild type, with an ovarian cancer that started with single cerebellar metastasis. CONCLUSION: Brain metastases in ovarian cancer are rare and complex for diagnosis and management. This case focuses both on diagnosis and treatment, emphasizing the importance of a multimodal approach in a multidisciplinary team.

Ki67 as a Predictor of Response to PARP Inhibitors in Platinum Sensitive BRCA Wild Type Ovarian Cancer: The MITO 37 Retrospective Study.

BACKGROUND: There is compelling need for novel biomarkers to predict response to PARP inhibitors (PARPi) in BRCA wild-type (WT) ovarian cancer (OC). METHODS: MITO 37 is a multicenter retrospective study aiming at correlating Ki67 expression at diagnosis with a clinical outcome following platinum treatment and PARPi maintenance. Clinical data were collected from high grade serous or endometroid BRCAWT OC treated with niraparib or rucaparib maintenance between 2010-2021 in 15 centers. Ki67 expression was assessed locally by certified pathologists on formalin-fixed paraffin embedded (FFPE) tissues. Median Ki67 was used as a cut-off. RESULTS: A total of 136 patients were eligible and included in the analysis. Median Ki67 was 45.7% (range 1.0-99.9). The best response to platinum according to median Ki67 was 26.5% vs. 39.7% complete response (CR), 69.1% vs. 58.8% partial response (PR), 4.4% vs. 1.5% stable disease (SD). The best response to PARPi according to median Ki67 was 19.1% vs. 36.8% CR, 26.5% vs. 26.5% PR, 26.5 vs. 25% SD, 27.9% vs. 16.2% progressive disease (PD). No statistically significant differences in progression free survival (PFS) and overall survival (OS) were identified between low and high Ki67. PFS and OS are in line with registration trials. CONCLUSIONS: Ki67 at diagnosis did not discriminate responders to PARPi.

Retrospective Analysis of the Correlation of MSI-h/dMMR Status and Response to Therapy for Endometrial Cancer: RAME Study, a Multicenter Experience.

BACKGROUND: There is poor evidence regarding sensitivity to chemotherapy in endometrial cancer (EC) based on microsatellite instability (MSI)/mismatch repair (MMR) status. METHODOLOGY: The RAME study is a retrospective analysis aiming to assess response to chemotherapy in MSI-high (h)/deficient (d) MMR and MSI-low (l)/proficient (p) MMR EC patients. Primary endpoints were recurrence-free survival (RFS) for patients with localized disease and progression-free survival (PFS) and overall survival (OS) in patients with advanced/recurrent disease. RESULTS: A total of 312 patients treated between 2010 and 2022 in four high-volume Multicenter Italian Trial in Ovarian cancer and gynecological malignancies (MITO) centers were selected. In total, 239 patients had endometrioid EC (76.6%), 151 had FIGO stage I at diagnosis (48.9%) and 71 were MSI-h/dMMR (22.8%). Median age was 65 (range 31-91) years. Among patients with localized disease, median RFS was 100.0 months (95% CI 59.4-140.7) for MSI-l/pMMR and 120.9 months (60.0-181.8) for MSI-h/dMMR (p = 0.39). Seventy-seven patients received first-line chemotherapy for advanced/recurrent disease. Patients with MSI-h/dMMR ECs had a significantly worse OS (p = 0.039). In patients receiving platinum-based chemotherapy, no statistically significant differences in PFS (p = 0.21) or OS (p = 0.057) were detected, although PFS and OS were numerically longer in the MSI-l/pMMR population. CONCLUSIONS: Patients with metastatic MSI-h/dMMR EC receiving first-line chemotherapy had a significantly worse OS.