Uterine Sarcoma Research Articles

UTERINE SAROMAS Retrospective Studies on 7 Cases at the Hassan II University Hospital in Fez

Introduction: Uterine sarcomas are rare tumors, representing less than 3% of malignant tumors of the female genital tract and between 3 and 7% of malignant tumors of the uterine body. They are a heterogeneous group of tumors comprising different histological subtypes, but with a generally identical evolutionary profile. Unlike uterine epithelial tumors, and apart from low-grade endometrial stromal sarcomas, uterine sarcomas have a poor prognosis. They have a high rate of recurrence (between 50 and 70%), local and especially metastatic (in approximately 70% of cases). The objective of our work is to specify the epidemiological characteristics of uterine sarcomas, the diagnostic difficulties faced by practitioners at the clinical, radiological and anatomopathological stages, the modalities of management as well as the different determinants of the prognosis of these rare tumors. Patients And Methods: Seven cases of uterine sarcomas treated in the gynecology - obstetrics II department at the Hassan II University Hospital in Fez between 2019 and 2023 were analyzed retrospectively. Results: The average age of our patients varies between 50 and 75 years with an average of 62.2 years. Of the 7 patients, 90% are multiparous, 100% menopausal. 78% of our patients consulted for metrorrhagia. On the paraclinical level, we performed a pelvic ultrasound for all patients, 80% of the results of which were in favor of an enlarged uterus with a heterogeneous echogenic intracavitary image, hysteroscopy in 04 patients for exploration of postmenopausal metrorrhagia and magnetic resonance imaging in 06 patients. The diagnosis was made at the preoperative stage in five patients. 71% of our patients benefited from surgical treatment. The anatomopathological analysis of the surgical specimens showed that 05, 07 patients benefited from adjuvant radiotherapy, while a combined chemotherapy/radiotherapy postoperatively was indicated in 02 patients. One patient presented a recurrence having ...

Case report: STRN3-NTRK3 fusion in uterine sarcoma with spleen metastasis: a new variant in the spectrum of NTRK-rearranged tumors

Neurotrophic tyrosine receptor kinase (NTRK) fusions are infrequent genetic events that can occur in various tumor types. Specifically, NTRK-rearranged sarcoma has been observed in pediatric mesenchymal tumors and, to a lesser extent, in adult mesenchymal tumors like fibrosarcoma. Recently, NTRK-rearranged uterine sarcoma (US) has been identified as a rare entity characterized by constitutive activation or overexpression of the TRK receptor, which plays a role in cell proliferation and differentiation. Since its initial description in 2018, only 46 cases of NTRK-rearranged US have been reported. In this context, herein we describe an exceptional case of an STRN3::NTRK3 fused US with histologically confirmed splenic metastasis. Notably, such localization has not been previously associated with pure uterine sarcomas in the literature. The fusion involved STRN3 (exon-3) and NTRK3 (exon-14) genes and was identified through next-generation sequencing analysis. Recognizing this specific molecular rearrangement is crucial, as it not only enables targeted therapy but also holds diagnostic significance in specific clinical scenarios.

Systemic hormone therapy after breast and gynecological cancers: an Italian expert group consensus opinion.

The specific Italian Group of Study of the Menopause formulated a consensus opinion on the use of estrogen therapy (ET) or combined estro-progestin hormone therapy (HT) after breast and gynecological cancers. This consensus is based on the risk of recurrence of the specific cancer during ET/HT, the presence of steroid receptors in cancer cells, the use of adjuvant hormone therapies and data on the use of ET/HT after cancer. The following positions were reached. ET/HT can be used after vulvar cancers and melanoma, but with great caution after the rare adenocarcinomas. ET/HT can be used after cervical cancer, but ET should be used with caution after adenocarcinomas. ET/HT can be used after International Federation of Obstetrics and Gynecology (FIGO) stage I-II estrogen-dependent endometrial cancers, except in Black women, and can probably be used after estrogen-independent endometrial cancers. ET/HT cannot be administered or should be used with great caution after most uterine sarcomas. ET/HT can probably be used after ovarian neoplasms except for granulosa cell tumors, and with great caution after low-grade serous ovarian carcinoma and serous borderline ovarian tumors. ET/HT can be used with great caution in women after estrogen receptor (ER)/progesterone receptor (PR)-positive breast cancer and is probably allowed after ER/PR-negative breast cancer.

Undifferentiated Uterine Sarcoma Causing Non-puerperal Uterine Inversion: A case report

Undifferentiated Uterine Sarcoma Causing Non-puerperal Uterine Inversion: A case report

Clinicopathologic Profile and Survival of Patients with Uterine Low Grade Endometrial Stromal Sarcoma

Clinicopathologic Profile and Survival of Patients with Uterine Low Grade Endometrial Stromal Sarcoma

The impact and correlation of lymphadenectomy with outcomes in patients with uterine sarcoma: A systematic review

Background: Sarcomas are an uncommon type of smooth muscle tumors in the uterus. The most popular form of treatment for uterine sarcomas is surgery. There is disagreement, nonetheless, over the best course of action for initial surgery. The aim of this systematic review was to examine the potential association between patient outcomes and the effects of LAD in individuals diagnosed with uterine sarcoma. Method: We conducted a comprehensive search of the PubMed database to identify publications assessing the impact of LAD on patients with uterine sarcoma that were published between 2009 and 2024. Based on the references in the studies that we included, we also conducted a search of the PubMed database. To find more relevant studies, the bibliographies of each pertinent paper were thoroughly reviewed. This review only includes studies that were published in English. Results: We included 7 papers in this systematic review, totaling 7896 patients. Four publications examined ESS, four studies examined LMS, two articles examined adenosarcoma, one study examined carcinosarcoma, and one study examined rhabdomyosarcoma. For individuals with low-grade ESS or adenosarcoma, LAD was not linked to a better prognosis. The survival rate was lower for patients with leiomyosarcoma who had LAD. Those who had LAD and had high-grade undifferentiated ESS fared better. LAD did not significantly correlate with RFS or OS in uterine sarcoma patients. Conclusion: Resection of lymph nodes or LAD has minimal potential benefit in terms of prognosis and clinical value.

Uterine mesenchymal tumours harboring the KAT6B/A::KANSL1 gene fusion represent a distinct type of uterine sarcoma based on DNA methylation profiles.

Uterine mesenchymal tumours harboring KAT6B/A::KANSL1 gene fusions typically exhibit histological and immunophenotypic overlap with endometrial stromal and smooth muscle tumours. To date it remains uncertain whether such neoplasms should be regarded as variants of smooth muscle or endometrial stromal neoplasm, or if they constitute a distinct tumour type. In this study we investigated DNA methylation patterns and copy number variations (CNVs) in a series of uterine tumours harboring KAT6B/A::KANSL1 gene fusions in comparison to other mesenchymal neoplasms of the gynecological tract. Unsupervised hierarchical clustering and t-SNE analysis of DNA methylation data (Illumina EPIC array) identified a distinct cluster for 8/13 KAT6B/A::KANSL1 tumours (herein referred to as core cluster). The other 5 tumours (herein referred to as outliers) did not assign to the core cluster but clustered near various other tumour types. CNV analysis did not identify significant alterations in the core cluster. In contrast, various alterations, including deletions at the CDKN2A/B and NF1 loci were identified in the outlier group. Analysis of the DNA methylation clusters in relation to histological features revealed that while tumours in the core KAT6B/A::KANSL1 cluster were histologically bland, outlier tumours frequently exhibited "high-grade" histologic features in the form of significant nuclear atypia, increased mitotic activity and necrosis. Three of the five patients with outlier tumours died from their disease while clinical follow-up in the remaining two patients was limited (less than 12months). In comparison, none of the 7 out of 8 patients with tumors in the core KAT6B/A::KANSL1 sarcoma cluster, where follow-up was available, died from disease. Furthermore, only 1 out of 7 patients recurred (mean follow-up of 30months). In conclusion, KAT6B/A::KANSL1 uterine sarcoma is a molecularly unique type of uterine tumour that should be recognized as a distinct entity. These tumors typically exhibit low-grade histologic features but are occasionally morphologically high-grade; the latter have a DNA methylation profile different from the typical low-grade neoplasms and may be associated with aggressive behaviour.

Uterine Sarcoma or Degenerating Fibroid? Validating the New Consensus Magnetic Resonance Imaging Algorithm for Evaluating Atypical Uterine Masses.

The aim of the study is to assess the validity of a recently published consensus magnetic resonance imaging (MRI) diagnostic algorithm for differentiating degenerating leiomyomas from uterine sarcomas and other atypical appearing uterine malignancies. Atypical uterine masses on pelvic MRI were identified using a radiology report search engine and teaching files with the keywords "atypical leiomyoma," "atypical fibroid," and "sarcoma." All cases were pathology-proven. Two radiologists blinded to clinical, surgical, and pathologic reports retrospectively and independently reviewed 40 pelvic MRI examinations dated 1/2007-9/2022 to determine whether the masses appeared benign or malignant, using the 2022 consensus atypical uterine mass flow chart. Imaging features assessed included intermediate/high signal intensity (SI) at T2-weighted imaging, high diffusion weighted imaging SI (equal or higher SI than endometrium or lymph nodes on high b value imaging), apparent diffusion coefficient (ADC) value ≤0.905 × 10-3 mm2/s, peritoneal metastases, and abnormal lymph nodes. Among the 40 atypical uterine mass cases reviewed, 24 masses were benign (22 leiomyomas, 1 adenomyoma, and 1 borderline ovarian tumor) and 16 masses were malignant (6 leiomyosarcomas, 6 carcinosarcomas, 2 endometrial stromal sarcomas, 1 high-grade adenosarcoma, and 1 low-grade uterine sarcoma). Sensitivity, specificity, positive predictive value, and negative predictive value of whether a mass was benign or malignant were 75%, 95.8%, 92.3%, and 85% for reader 1, and 81.2%, 91.7%, 86.7%, and 88% for reader 2, respectively. Interrater agreement was strong, with a kappa statistic of 0.89. When excluding nonleiomyosarcoma uterine malignancies, sensitivity and negative predictive value improved to 100%. The new consensus pelvic MRI algorithm for evaluating atypical uterine masses has good specificity, sensitivity, positive predictive value, and negative predictive value for determining malignancy, particularly for uterine sarcomas that are leiomyosarcomas. However, if ADC value is near but not below 0.905 × 10-3 mm2/s, the mass may still be malignant, especially if a b value lower than 1000 is used. If the atypical uterine mass is predominantly endometrial, morphological features on T2 and postgadolinium sequences should guide suspicion, as some atypical appearing nonleiomyosarcoma uterine malignancies may have an ADC value greater than 0.905 × 10-3 mm2/s.

A Simple Eco-Friendly HPLC-PDA Method for the Simultaneous Determination of Paclitaxel and Seliciclib in Plasma Samples for Assessing Their Pharmacodynamics and Pharmacokinetics in Combination Therapy for Uterine Sarcoma.

Background/Objectives: Uterine sarcoma, a rare cancer originating in the smooth muscle of the uterus, exhibits high rates of recurrence and metastasis. It represents one of the most challenging types of cancer due to its chemorefractory nature, showing little response to conventional chemotherapy methods and displaying a relative survival rate of 30-40%. A potentially promising approach for treating uterine sarcoma involves combination therapy with paclitaxel (PAC), a microtubule-targeting agent, and seliciclib (SEL), a cyclin-dependent kinase inhibitor. SEL has been identified as a drug that can enhance the effectiveness of PAC through synergistic effects. To further refine this treatment strategy, an efficient analytical tool capable of simultaneously measuring the concentrations of PAC and SEL in blood plasma is needed. This tool would make it easier to study the pharmacokinetic interactions of potential drugs and assist in monitoring therapy when administering this combination treatment. Regrettably, a method meeting these specific requirements has not been documented in the existing literature. Methods: This article introduces the first HPLC technique employing a PDA detector to concurrently measure PAC and SEL levels in plasma. The methodology underwent validation in accordance with the ICH standards for validating bioanalytical methods. Results: The method exhibited linearity in the concentrations ranging from 0.8 to 100 µg mL-1 for both PAC and SEL. The limits of quantification were determined and found to be 1.34 and 1.25 µg mL-1 for PAC and SEL, respectively. All the other validation criteria conformed to the ICH validation standards. The HPLC-PDA method was successfully employed to quantify both PAC and SEL in plasma samples with a high level of reliability (in terms of accuracy and precision). The eco-friendliness of the approach was verified using three thorough assessments. This technique serves as a valuable asset in establishing the correct dosage and administration schedule for the combined treatment involving PAC and SEL, ensuring the desired therapeutic effects and safety in managing uterine sarcoma. Conclusions: The proposed HPLC-PDA method is the first reliable and eco-friendly method developed to simultaneously determine PAC and SEL in high-throughput plasma samples in clinical laboratories.

Individualized evaluation of risk and prognosis in uterine leiomyosarcoma patients with synchronous distant metastases: a real-world retrospective study.

Uterine leiomyosarcoma (uLMS) accounts for roughly 70% of all uterine sarcomas, with recurrence and mortality rates notably higher than those of other uterine tumors. The prognosis of uLMS patients who have distant metastases remains poor. The objective of this study was to determine independent risk variables related to distant metastases in patients with uLMS and prognostic factors for those with distant metastases. Subsequently, two practical nomograms were developed and validated to assess the probability of distant metastases and predict survival outcomes for these with distant metastases, respectively. A real-world retrospective study was carried out using data from patients diagnosed with primary uLMS in the Surveillance, Epidemiology, and End Results (SEER) database spanning the years 2010 to 2015. Univariate andmultivariate logistic regression analyses were utilized to identify clinicopathological characteristics related to the risk of distant metastases, while univariate and multivariate Cox regressions were employed to determine prognostic factors. Then, a risk nomogram incorporating independent risk variables and a prognostic nomogram integrating independent prognostic factors were established in the training cohort and validated for accuracy in the validation cohort, respectively. Receiver operating characteristic (ROC) curves, area under the curve (AUC), and calibration curves were utilized to measure the accuracy of nomograms, while decision curve analysis (DCA) curves were employed to assess their clinical benefit capacity. Based on the median total point derived from the prognostic nomogram, patients were stratified into high- and low-risk groups. The differentiation ability of the prognostic nomogram was evaluated using Kaplan-Meier survival analysis with the log-rank test. The study encompassed 1,362 patients diagnosed with uLMS, among whom 337 cases (24.7%) manifested synchronous distant metastases at the initial diagnosis. Univariate and multivariate logistic regression analyses identified race, histological grade, T stage, N stage, tumor size, surgery, and chemotherapy as independent risk factors for distant metastases in uLMS patients. The outcomes of both univariate and multivariate Cox analyses indicated that surgery and chemotherapy emerged as independent protective factors for prognosis in uLMS patients with distant metastases, whereas higher histological grade and T stage were identified as independent risk factors. The risk nomogram incorporating independent risk variables and the prognostic nomogram integrating independent prognostic factors could respectively predict the risk of metastases and the prognosis very effectively in both training and validation cohorts. In summary, we developed the novel well-validated risk nomogram to precisely assess the probability of metastases in uLMS patients and prognostic nomogram to predict the prognosis of those with distant metastases, providing decision-making guidance for tailoring individualized clinical management of these patients.

Clinicopathological and survival analysis for patients with uterine sarcoma treated following surgery for presumed benign disease

ObjectivesTo investigate the clinicopathological characteristics and prognosis of patients with uterine sarcoma treated following surgery for presumed benign disease.MethodsWe identified all patients with uterine sarcoma found incidentally after primary surgery for presumed benign disease who presented to our institution and received re-exploration for completion surgery from January 1, 2004 to January 1, 2021. We analyzed the clinicopathological characteristics and prognosis.ResultsOverall, 95 patients were included in our study. For the initial surgery, myomectomy was performed in 50 (52.6%, 50/95) patients, hysterectomy was performed in 45 (47.4%, 45/95) patients. All patients were re-explored to complete the staging operation. The median time to the staging surgery was 40 days (range 15–90 days). There were 29 patients (30.5%, 29/95) had remnant sarcomas, with 17 patients (17/95, 17.9%) on the remaining uterus, 9 patients (9/95, 9.5%) had disseminated diseases, and 4 patients (4/95, 4.2%) had positive lymph nodes. About 40 patients (42.1%) received adjuvant chemotherapy, 55.2% (16/29) and 36.4% (24/66) patients with/without remnant diseases received adjuvant chemotherapy, respectively (P = 0.087). The median follow-up duration was 76.7 months (IQR: 34.8-118.1 months). And 17 patients (17.9%) had recurrence following re-exploration surgery. 5-year progression-free survival (PFS) and 5-year overall survival (OS) for the entire cohort was 81.7% and 92.1%, respectively. Patients with remnant sarcomas had a tendency towards a worse 5-year PFS and 5-year OS, compared with those without (5-year PFS: 75.6% vs. 84.5%, P = 0.224; 5-year OS: 85.5% vs. 95.1%, P = 0.217). Patients with disseminated diseases had a worse 5-year OS (62.5% vs. 95.1%, P = 0.007) and non-significantly worse 5-year PFS (64.8% vs. 83.4%, P = 0.153) compared with those without.ConclusionsPatients with uterine sarcoma treated following surgery for presumed benign disease have a favorable survival. Patients with disseminated diseases had a worse 5-year OS compared with those without. Surgical re-exploration may be valuable for removing remnant sarcomas and disseminated diseases.

Prognosis and treatment of uterine sarcoma found incidentally after myomectomy

ObjectiveTo determine prognosis and factors associated with survival of women with uterine sarcoma found incidentally after myomectomy. MethodsWe performed a retrospective study for patients who had previously undergone myomectomy for presumed benign uterine fibroid disease and were found to have uterine confined sarcoma after myomectomy surgery. ResultsIn total, 50 patients were identified. There were 23 (46.0 %) patients undergoing myomectomy were performed by minimal invasive surgery: laparoscopic (Lap, n = 22, 44.0 %) or transvaginal (TV, n = 1, 2.0 %) approach; while, 24 (48.0 %) and 3 (6.0 %) patients had myomectomy through abdominal (Abd) or hysteroscopic (Hys) approach. All patients received the re-exploration and staging surgery in our center. The median time from myomectomy to the staging surgery was 43 days (range 15–90 days). 17 patients had remnant sarcomas on the remaining uterus and 6 patients had disseminated disease after re-exploration. In the entire cohort, 5-year RFS and 5-year OS was 79.4 % and 88.0 %, respectively. Patients who received initial Lap/TV myomectomy had a tendency towards a worse 5-year RFS compared with Abd/Hys approach (63.0 % vs 88.9 %, P = 0.080). No difference in 5-year OS was found between the two groups (90.3 % vs 91.8 %, P = 0.768). For stage I disease (n = 44), patients who received Lap/TV myomectomy had a worse 5-year RFS compared with Abd/Hys approach (58.3 % vs 95.7 %, P = 0.009). No difference in 5-year OS was found (P = 0.121). ConclusionPatients with incidental uterine sarcoma who received primary Lap/TV myomectomy may have a worse RFS. Re-exploration can detect remnant or disseminated sarcomas.

Survival Trends for Uterine Sarcomas from a Tertiary Center: The Oxford Experience.

Uterine sarcomas are rare and aggressive gynecological malignancies. We evaluated the epidemiology, treatment outcomes and survival rates in uterine sarcoma patients managed in our institute. The medical records of women with histology proven uterine sarcoma, including leiomyosarcoma (LMS), adenosarcoma (ADS), and endometrial stromal sarcoma (ESS), treated at our institution from February 2010 to February 2022, were analyzed. In total, 41 patients were identified. In detail, LMS, ADS, and high-grade and low-grade ESS were identified, respectively, in 60.9%, 19.5%, 12.1%, and 7.3% of the cases. The majority of women affected by LMS (72%) underwent primary surgery and 40% of them also received adjuvant chemotherapy. A surgical approach was the preferred mode of treatment in 83% of the recurrences. The median OS (overall survival), DFS (disease free survival), and PFS (progression free survival) for the LMS group were 25, 44.5, and 8 months, respectively. The 5-year survival rates for LMS, ADS, and ESS groups were 30.5%, 100% and 37.5%, respectively. The 5-year survival for LMS was found to be significantly worse than for other histology types (p = 0.016). Our study provides valuable data for the evaluation of treatment strategies and survival trends among these rare cancers. The management and follow-up planning of each subtype requires a thorough patient-focused multidisciplinary discussion.

216P β-catenin is a potential prognostic biomarker in uterine sarcoma

216P β-catenin is a potential prognostic biomarker in uterine sarcoma

Letter to the Editor for the article 'Prognosis of uterine and extrauterine low-grade endometrial stromal sarcoma: an observational cohort study'.

Letter to the Editor for the article 'Prognosis of uterine and extrauterine low-grade endometrial stromal sarcoma: an observational cohort study'.

Management and prognosis of uterine sarcoma in elderly

Management and prognosis of uterine sarcoma in elderly

Soft Tissue Sarcomas: Epidemiologic Trends at King Abdulaziz University Hospital in Jeddah

Objectives: We aim to enhance the understanding of soft tissue sarcomas (STS) within the Saudi population, guiding better diagnosis, treatment strategies, and healthcare resource allocation for this rare but challenging cancer type. Methods: Retrospective data of 160 patients at King Abdulaziz University Hospital (2013-2023) were examined for demographics, anatomical sites, and diagnoses of STS. Statistical analysis in RStudio (R v4.3.1) utilized Fisher's exact and chi-squared tests for categorical variables (p<0.05), while continuous variables were summarized by medians and interquartile range. Results: We included patients with STS, evenly split between males and females (median age: 47 years) Significant differences were observed between age groups: younger patients (<50 years) more commonly had rhabdomyosarcoma and synovial sarcoma, while older patients (≥50 years) showed higher rates of dedifferentiated liposarcoma, Kaposi sarcoma, and leiomyosarcoma. Sarcoma locations varied, with the thigh, retroperitoneum, and head and neck being prominent sites. Higher frequencies of Kaposi sarcoma and skin sarcomas were noted in males, and leiomyosarcoma and uterine sarcomas exclusively in females. Conclusion: The study highlights significant sex and age disparities in the diagnosis and distribution of STS among Saudi patients. Rhabdomyosarcoma emerges as the most frequent subtype, influenced by factors such as genetic predisposition and advanced diagnostic capabilities. Understanding these demographic variations is crucial for developing targeted treatment strategies tailored to the unique needs of different patient groups. Further research into the underlying biological and environmental factors driving these disparities is essential for advancing sarcoma care and improving patient outcomes in Saudi Arabia.

ERBB2/ ERBB3-mutated S100/ SOX10-positive unclassified high-grade uterine sarcoma: first detailed description of a novel entity.

With the increasing use of innovative next generation sequencing (NGS) platforms in routine diagnostic and research settings, the genetic landscape of uterine sarcomas has been dynamically evolving during the last two decades. Notably, the majority of recently recognized genotypes in uterine sarcomas represent gene fusions, while recurrent oncogene mutations of diagnostic and/ or therapeutic value have been rare. Recently, a distinctive aggressive uterine sarcoma expressing S100 and SOX10, but otherwise lacking diagnostic morphological, immunophenotypic and molecular features of other uterine malignancies has been presented in a scientific abstract form (USCAP, 2023), but detailed description and delineation of the entity is still missing. We herein describe two high-grade unclassified uterine sarcomas characterized by spindle to round cell morphology and diffuse expression of S100 and SOX10, originating in the uterine body and cervix of 53- and 45-year-old women and carrying an ERBB3 (p.Glu928Gly) and an ERBB2 (p.Val777Leu) mutation, respectively. Both tumors harbored in addition genomic HER2 amplification, ATRX mutation and CDKN2A deletion. Methylation studies revealed a methylome most similar to MPNST-like tumors, but distinct from melanoma, MPNST, clear cell sarcoma, and endometrial stromal sarcoma. Case 1 died of progressive peritoneal metastases after multiple trials of chemotherapy 47months after diagnosis. Case 2 is a recent case who presented with a cervical mass, which was biopsied. This study defines a novel heretofore unrecognized aggressive uterine sarcoma with unique phenotypic and genotypic features. Given the potential value of targeting HER2, recognizing this tumor type is mandatory for appropriate therapeutic strategies and for better future delineation of the entity.

Unraveling the Role of Bromodomain and Extra-Terminal Proteins in Human Uterine Leiomyosarcoma.

Uterine leiomyosarcoma (uLMS) is the most common type of uterine sarcoma, associated with poor prognosis, high rates of recurrence, and metastasis. Currently, the molecular mechanism of the origin and development of uLMS is limited. Bromodomain and extra-terminal (BET) proteins are involved in both physiological and pathological events. However, the role of BET proteins in the pathogenesis of uLMS is unknown. Here, we show for the first time that BET protein family members, BRD2, BRD3, and BRD4, are aberrantly overexpressed in uLMS tissues compared to the myometrium, with a significant change by histochemical scoring assessment. Furthermore, inhibiting BET proteins with their small, potent inhibitors (JQ1 and I-BET 762) significantly inhibited the uLMS proliferation dose-dependently via cell cycle arrest. Notably, RNA-sequencing analysis revealed that the inhibition of BET proteins with JQ1 and I-BET 762 altered several critical pathways, including the hedgehog pathway, EMT, and transcription factor-driven pathways in uLMS. In addition, the targeted inhibition of BET proteins altered several other epigenetic regulators, including DNA methylases, histone modification, and m6A regulators. The connections between BET proteins and crucial biological pathways provide a fundamental structure to better understand uterine diseases, particularly uLMS pathogenesis. Accordingly, targeting the vulnerable epigenome may provide an additional regulatory mechanism for uterine cancer treatment.

The value of multiparametric MRI-based habitat imaging for differentiating uterine sarcomas from atypical leiomyomas: a multicentre study.

To explore the feasibility of multiparametric MRI-based habitat imaging for distinguishing uterine sarcoma (US) from atypical leiomyoma (ALM). This retrospective study included the clinical and preoperative MRI data of 69 patients with US and 225 patients with ALM from three hospitals. At both the individual and cohort levels, the K-means and Gaussian mixture model (GMM) algorithms were utilized to perform habitat imaging on MR images, respectively. Specifically, T2-weighted images (T2WI) and contrast-enhanced T1-weighted images (CE-T1WI) were clustered to generate structural habitats, while apparent diffusion coefficient (ADC) maps and CE-T1WI were clustered to create functional habitats. Parameters of each habitat subregion were extracted to construct distinct habitat models. The integrated models were constructed by combining habitat and clinical independent predictors. Model performance was assessed using the area under the curve (AUC). Abnormal vaginal bleeding, lactate dehydrogenase (LDH), and white blood cell (WBC) counts can serve as clinical independent predictors of US. The GMM-based functional habitat model at the cohort level had the highest mean AUC (0.766) in both the training and validation cohorts, followed by the GMM-based structural habitat model at the cohort level (AUC = 0.760). Within the integrated models, the K-means functional habitat model based on the cohort level achieved the highest mean AUC (0.905) in both the training and validation cohorts. Habitat imaging based on multiparametric MRI has the potential to distinguish US from ALM. The combination of clinical independent predictors with the habitat models can effectively improve the performance.