Leiomyosarcoma Research Articles

Gamma secretase inhibitors, in combination with cytotoxic agents, decrease migration and invasion of uterine leiomyosarcoma

Gamma secretase inhibitors, in combination with cytotoxic agents, decrease migration and invasion of uterine leiomyosarcoma

Notch inhibition with γ-secretase inhibitor increases apoptosis of uterine leiomyosarcoma cells

Notch inhibition with γ-secretase inhibitor increases apoptosis of uterine leiomyosarcoma cells

Preoperative identification from occult leiomyosarcomas in laparoscopic hysterectomy and laparoscopic myomectomy: accuracy of the ultrasound scoring system (PRESS-US).

To assess the diagnostic performance and inter-observer agreement of a PREoperative sarcoma scoring based on ultrasound (PRESS-US) in differentiating uterine leiomyosarcoma (uLMS) from leiomyoma (LM). We conducted a retrospective evaluation of patients who underwent surgery and received standardized ultrasound examinations due to the presence of uterine myoma-like masses. Histological diagnosis was used as the reference standard. The masses were analyzed using morphological uterus sonographic assessment criteria, and the diagnostic accuracy of PRESS-US was evaluated using ROC curve analysis. Kappa (κ) statistics were used to assess the inter-observer agreement between a less experienced and an expert radiologist. Among the 646 patients, 632 (97.8%) were diagnosed with LM, and 14 (2.2%) had uLMS. The malignancy rates for low-risk and high-risk patients were 0.35% and 13.48%, respectively. The optimal PRESS-US cutoff was 17.5, resulting in an AUC of 89.7% (95% CI, 0.79-1.00), with a sensitivity of 85.7% and a specificity of 87.8%. The inter-observer agreement between a less experienced and an expert radiologist was excellent (κ = 0.811, P < 0.001). PRESS-US provides effective risk stratification for uLMS for radiologists with different levels of experience, with high reliability. Subgrouping high-risk patients helps in better risk stratification.

Clinical characteristics and treatment outcomes of women with recurrent uterine leiomyosarcoma

ObjectiveTo determine the clinical characteristics and treatment outcomes of women with recurrent uterine leiomyosarcoma (uLMS).MethodsWe conducted a retrospective cohort study to evaluate the clinical characteristics and survival of women with recurrent uLMS and identify prognostic factors.ResultsOverall, 71 patients with first recurrence of uLMS were included in our study. 19 patients (26.8%) received systemic therapy and 52 patients (73.2%) received secondary cytoreductive surgery (SCS). In SCS subgroup (n = 52), a complete resection with no residual disease was performed in 47 patients (90.4%). 38.5% (20/52) patients received non-reproductive organ surgeries. 10 (19.2%) patients had received thoracic surgery because of lung-only recurrence. Bowel, bladder surgery was performed in 8 (15.4%), 3 (5.8%) patients, respectively. 1 (1.9%) patient had received liver surgery. The median follow-up duration was 38.7 months (range: 2.7-317.6 months). 41 (57.7%) patients died during follow-up. 5-year OS for the entire cohort was 52.9%. Patients experienced first recurrence after initial diagnoses within 12 months (n = 24) had a worse 5-year OS than those after 12 months (n = 47) (17.0% vs. 69.1%, P < 0.001). 5-year OS for the SCS and non-SCS subgroup was 62.0% and 28.0%, respectively (P < 0.001). Multivariate analysis showed time to fist recurrence within 12 months (HR = 4.60, 95% CI: 1.49–14.4, P = 0.008) was an independent predictor of decreased 5-year OS in SCS subgroup.ConclusionsSCS is an important treatment choice for recurrent uLMS and seems to have benefited patients. Time to fist recurrence within 12 months is an independent predictor of decreased 5-year OS in SCS subgroup.

Phase 2 trial of avelumab in combination with gemcitabine in advanced leiomyosarcoma as a second-line treatment (EAGLES, Korean Cancer Study Group UN18-09).

In this single-arm, multicenter, phase 2 trial, the authors evaluated the efficacy and safety of avelumab plus gemcitabine in patients with leiomyosarcoma (LMS) who failed on first-line chemotherapy. Patients with advanced LMS received avelumab 10 mg/kg on days 1 and 15 (for up to 24 months) plus gemcitabine 1000 mg/m2 on days 1, 8, and 15 of a 28-day cycle until they developed disease progression or intolerable toxicity. The primary end point was the objective response rate (ORR). In total, 38 patients were enrolled. Of these, 35 patients were evaluable, and the ORR was 20% (95% confidence interval; [CI], 8%-37%). The disease control rate was 71%, and the median duration of response was 21.8 months (range, 7.6 to ≥43.3 months). The median progression free-survival was 5.6 months (95% CI, 4.5-6.8 months), and the median overall survival was 27.5 months (95% CI, 20.4-34.6 months). Grade 3-4 adverse events occurred in 70% of patients, of which neutropenia was the most common (54%). Immune-mediated adverse events occurred in five patients (14%; hypothyroidism, n=3; hepatitis, n=2). Patients who had a higher density of tumor-infiltrating lymphocytes (greater than the median) exhibited better ORR (35% vs. 8%; p=.104), progression-free survival (median, 7.3 vs. 3.3 months; p=.024), and overall survival (median, not reached vs. 21.5 months; p=.027). The combination of avelumab and gemcitabine demonstrated promising efficacy and manageable safety in patients with advanced LMS who progressed on first-line therapy. Tumor-infiltrating lymphocyte density may be an important factor in predicting the response to combining immunotherapy with chemotherapy.

Exploring Immunohistochemical Profiling in High-Grade Endometrial Stromal Sarcoma - A Case Study

Abstract Introduction/Objective High grade endometrial stromal sarcoma (HGESS) is a rare and aggressive tumor of endometrial stromal origin comprising about 0.2% of all uterine malignancies. It is often misdiagnosed preoperatively as uterine leiomyoma, leiomyosarcoma or endometrial carcinoma due to lack of well defined clinical and radiological features. We present an unusual case of HGESS with fibroid uterus and abnormal vaginal bleeding. Methods/Case Report A 73-year-old female with a past medical history of uterine fibroids presented with abnormal vaginal bleeding for 6 months. Her MRI uterus revealed enlarged uterus measuring 6.8 X 9.9 X 9.3 cm, multiple fibroids, and endometrial thickness of 4 mm. Hysteroscopic dilation and curettage revealed endometrial polyp and submucosal fibroid. Histopathology of submucosal fibroid revealed loosely cohesive tumor cells with high nuclear/cytoplasmic ratio, scant cytoplasm, and large prominent nucleoli, arranged in solid sheets with myxoid stroma. No glandular formation was identified. Tumor cell necrosis, bizarre tumor cells, and markedly increased mitotic activity, including atypical mitotic figures were present. Immunohistochemistry (IHC) revealed tumor cells diffusely positive for smooth muscle actin, CD10, p53, negative for AE1/AE3, CK7, cam5.2, EMA, ER, PR, desmin, and caldesmon. Ki-67 labels close to 50% of the tumor cells. Combined morphologic and IHC features favored the diagnosis of high-grade sarcoma, including leiomyosarcoma and HGESS. However, the possibility of carcinosarcoma (CS) could not be ruled out. Patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy. Final histopathological diagnosis revealed HGESS, pT1b. Lack of carcinomatous component and negative IHC staining for CK7, CAM 5.2, AE1/AE3 ruled out CS. IHC showed tumor cells diffusely positive for CD10, actin, desmin and CD 56, focally positive for caldesmon, cyclin D1 and CD 117 and negative for DOG 1, further supporting the diagnosis for HGESS over leiomyosarcoma. Results (if a Case Study enter NA) NA Conclusion Definitive diagnosis of HGESS is achieved through histology and IHC. An appropriate panel of IHC markers is essential to differentiate between endometrial stromal tumors from leiomyosarcoma and CS. Accurate diagnose of this rare clinical entity is critical especially in its initial stages owing to its poor prognosis and aggressive nature.

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.

Endoscopic endonasal approach for resection of sellar leiomyosarcoma metastasis: illustrative case.

Leiomyosarcoma (LMS) is a rare neoplasm that arises from tissues of embryonic mesodermal origin. Primary tissues of origin can include smooth muscle cells of the abdominopelvic viscera, blood vessels, or arrector pili muscles. LMS is known to metastasize to the lungs, with few reported cases of spread to the central nervous system. A 66-year-old male with cutaneous LMS of the left forearm with metastases to the lungs and kidney that had been treated with chemoradiation presented with worsening headaches. Magnetic resonance imaging revealed a sellar lesion. An endocrine workup was unremarkable. Imaging over 6 months revealed rapid interval growth. Positron emission tomography demonstrated moderate uptake. Given the rapid growth, the patient was offered an endoscopic endonasal approach for resection. Pathology confirmed LMS. To the authors' knowledge, this is the first documented case of LMS metastasis to the sella. Pituitary carcinoma or metastases to the sellar region should be in the differential among patients with sellar region tumors with a rapid growth rate, bony erosion, or findings of lesions in the upper cervical lymph nodes or soft tissue. Tumors that show significant interval growth should raise suspicion for nonadenomatous lesions, and surgical intervention should be considered even in the absence of endocrinological dysfunction or cranial neuropathies. https://thejns.org/doi/10.3171/CASE2435.

Disruptions in antigen processing and presentation machinery on sarcoma

BackgroundThe antigen processing machinery (APM) plays a critical role in generating tumor-specific antigens that can be recognized and targeted by the immune system. Proper functioning of APM components is essential for presenting these antigens on the surface of tumor cells, enabling immune detection and destruction. In many cancers, defects in APM can lead to immune evasion, contributing to tumor progression and poor clinical outcomes. However, the status of the APM in sarcomas is not well characterized, limiting the development of effective immunotherapeutic strategies for these patients.MethodsWe investigated 126 patients with 8 types of bone and soft tissue sarcoma operated between 2001–2021. Tissue microarrays mapped 11 specific areas in each case. The presence/absence of APM protein was determined through immunohistochemistry. Bayesian networks were used.ResultsAll investigated sarcomas had some defects in APM. The least damaged component was HLA Class I subunit β2-microglobulin and HLA Class II. The proteasome LMP10 subunit was defective in leiomyosarcoma (LMS), myxoid liposarcoma (MLPS), and dedifferentiated liposarcoma (DDLPS), while MHC I transporting unit TAP2 was altered in undifferentiated pleomorphic sarcoma (UPS), gastrointestinal stromal tumor (GIST), and chordoma (CH). Among different neoplastic areas, high-grade areas showed different patterns of expression compared to high lymphocytic infiltrate areas. Heterogeneity at the patient level was also observed. Loss of any APM component was prognostic of distant metastasis (DM) for LMS and DDLPS and of overall survival (OS) for LMS.ConclusionSarcomas exhibit a high degree of defects in APM components, with differences among histotypes and tumoral areas. The most commonly altered APM components were HLA Class I subunit β2-microglobulin, HLA Class I subunit α (HC10), and MHC I transporting unit TAP2. The loss of APM components was prognostic of DM and OS and clinically relevant for LMS and DDLPS. This study explores sarcoma molecular mechanisms, enriching personalized therapeutic approaches.

Ultrasonographic Performance and Clinical Analysis of Ultrasound in the Diagnosis of Uterine Fibroids

Objective: To assess ultrasound’s ultrasonographic performance and clinical value in diagnosing uterine fibroids. Methods: 60 patients with suspected uterine fibroids admitted to the hospital between March 2021 and March 2024 were selected for this study. Abdominal B-mode ultrasound was used as the gold standard to detect pathological findings, and the results were compared and analyzed. Results: 54 patients were diagnosed after the gold standard, and the results of abdominal B-mode ultrasound were positive predictive value: 96.29%; negative predictive value: 66.67%; accuracy: 93.33%; sensitivity: 96.29%; specificity: 66.67%. Among 60 patients examined by B-mode ultrasound, there were a total of 54 patients who were diagnosed by the gold standard, and 19 cases of uterine leiomyosarcoma were confirmed by the detection of uterine leiomyosarcoma by the gold standard, and B-mode ultrasound (94.73%); 21 cases of cervical leiomyoma were confirmed by gold standard test and 20 cases of cervical leiomyoma were diagnosed by ultrasound (95.24%); 14 cases of mixed leiomyoma were confirmed by gold standard test and 14 cases of mixed leiomyoma were diagnosed by ultrasound (100.00%). Conclusion: Using abdominal ultrasound to examine patients with uterine fibroids can significantly improve the efficiency of diagnosis and treatment and provide a strong scientific basis for subsequent treatment decisions.

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.

1727MO Can proteomics predict metastatic relapse in leiomyosarcoma (LMS)? Development of an 8 protein signature in a >350 sample study including a validation cohort

1727MO Can proteomics predict metastatic relapse in leiomyosarcoma (LMS)? Development of an 8 protein signature in a >350 sample study including a validation cohort

A rare case report of paratesticular leiomyosarcoma

A leiomyosarcoma (LMS) is a malignant mesenchymal tumor of soft tissue that rarely presents in the scrotal region. This case report describes a primary paratesticular LMS originating in the dartos layer of the scrotum in a symptomatic 37-year-old male with a history of hypertension, generalized seizure disorder post-excision of meningioma, and an extensive family history of cancer. Primary paratesticular LMSs in the superficial dartos layer are exceedingly rare. Given the rarity of this particular type of LMS, this case report includes a discussion on its prevalence and incidence. The rarity of this tumor also warrants a review of the literature and related cases to inform the treatment plan and enhance understanding of these oncologic conditions.

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.

NNMT overexpression is an adverse prognostic factor in uterine leiomyosarcoma.

Uterine leiomyosarcomas (uLMS) are extremely rare high-grade tumors with a poor prognosis. Their etiopathogenesis remains largely unknown. The uterus is the most frequent site for LMS. uLMS and uterine leiomyoma (uLM) must frequently be differentiated in patients with a uterine mass. Nicotinamide N-methyltransferase (NNMT), a cytoplasmic protein, is involved in the progression and spread of a variety of cancer types. The expression of NNMT in a mesenchymal malignancy was not examined previously. This study represents the first investigation into NNMT expression in uLMS, uLM and benign uterine myometrium and correlates NNMT overexpression with worse prognosis in uLMS. The expression of NNMT was investigated by immunohistochemistry on formalin-fixed paraffin-embedded tissue of uLMS in 31 patients, uLM in seven patients and benign myometrial in 31 patients. The expression of NNMT in uLMS was markedly higher than in uLM and normal myometrial tissue (p < 0.001). The expression of NNMT in early stage uLMS was lower than in advanced stage disease (p = 0.034). NNMT expression was an independent prognostic factor in predicting recurrence-free survival in uLMS (p = 0.037). NNMT can aid in the preoperative differentiation of uLMS and uLM. The consequences of NNMT overexpression, such as the activation and inactivation of oncoproteins and tumor suppressor proteins, respectively, as well as the enrichment of the cancer stem cell population, overlap with the major mechanisms responsible for poor prognosis in mesenchymal tumors. NNMT may be investigated further in the context of antitumor treatment in patients with mesenchymal malignancies.

Osseous metastases of uterine leiomyosarcoma: Analysis of survival & surgical management

BackgroundUterine leiomyosarcoma represents a seldom-encountered subset within the spectrum of uterine malignancies. Occurrences of appendicular skeletal metastases in uterine leiomyosarcomas are infrequent. In this study, we examined patient surveys to elucidate the clinical characteristics and outcomes of individuals with uterine leiomyosarcoma exhibiting metastatic dissemination to these anatomical regions. We hypothesized that palliative surgical treatment would have no effect on survival in patients diagnosed with uterine leimyosarcoma with appendicular bone metastases. MethodsOne hundred fourteen patients diagnosed with uterine leiomyosarcoma and treated at the Department of Oncologic Orthopedics at XXX hospital from 2004 to 2021 met the criteria for inclusion in this retrospective cohort study. The study specifically encompassed patients with histopathologically confirmed appendicular bone metastases secondary to uterine leiomyosarcoma, who underwent either surgical intervention or conservative treatment. Exclusion criteria involved patients with exclusive vertebral bone metastases, as well as those lacking essential examination and follow-up data. Notably, the study included nine follow-up patients with at least 2 years of follow-up who developed appendicular skeletal metastases during the follow-up period. ResultsOf the 9 patients, 3 had humeral metastases, 2 had femoral metastases, 1 had femoral and diffuse pelvic metastases, and the other 3 had pelvic metastases. Bone metastases occurred at a mean of 33.3 ± 32.4 months (range 3 - 108) after the diagnosis. After bone metastasis, 6 patients died after an average of 40.3 ± 26.7 months (range 12–84 months). One patient with a pathologic fracture in the proximal humerus underwent resection arthroplasty, 1 patient with metastases in the proximal femur underwent resection arthroplasty, 2 patients with metastases to the femoral shaft underwent curettage-cementation (C&C) and intramedullary nailing, and 1 patient with persistent pelvic pain underwent C&C. No surgery was performed in the other patients. ConclusionIn patients diagnosed with uterine leiomyosarcomas, survival did not differ between palliative surgery and conservative treatment after appendicular bone metastases. Patient assessment should be individualized, and overall health should be evaluated before palliative surgery is performed. Level of EvidenceIV.

The Impact of Li-Fraumeni and Germline Retinoblastoma Mutations on Leiomyosarcoma Initiation, Outcomes, and Genetic Testing Recommendations.

Leiomyosarcomas (LMS) are clinically and molecularly heterogeneous, occurring mostly in sporadic but also syndromic settings. The role of pathogenic germline variants (PGV) as LMS drivers and their impact on outcomes remains uncertain. We performed a comprehensive clinicopathologic and molecular analysis using a tumor-normal DNA next-generation sequencing assay (Memorial Sloan Kettering-Integrated Mutational Profiling of Actionable Cancer Targets) of germline-associated LMS compared with sporadic LMS. Among 285 LMS [120 soft-tissue LMS (STLMS) and 165 uterine LMS (ULMS)] with germline testing, 78 (27%, 43 STLMS and 35 ULMS) cases harbored PGV, with 35/78 (45%) of PGV carriers showing biallelic inactivation of the corresponding gene in the tumor (26 STLMS and nine ULMS). The most frequent germline predispositions were TP53 (Li-Fraumeni syndrome; 17 patients, 16 in STLMS) and RB1 (retinoblastoma; 13 patients, 11 in STLMS). Germline TP53 and somatic RB1 alterations often co-occurred in the tumor andvice versa. Other biallelically inactivated PGV were enriched in DNA damage repair-related genes: CHEK2, MSH2, MSH6, RAD51D, BRCA2, and FANCA. Monoallelic PGV were mostly in ULMS and associated with co-occurring TP53 and RB1 somatic alterations. Patients with STLMS with biallelic but not monoallelic PGV were significantly younger than patients with sporadic STLMS (median ages 38 vs. 52 vs. 58 years). No differences in disease-specific or progression-free survival were observed in germline-associated versus sporadic LMS regardless of biallelic status. Although patients with ULMS had a relatively low proportion of PGV, a high percentage of patients with STLMS with PGV had tumor biallelic status, indicating that PGV drive tumorigenesis in these individuals. These findings have significant implications for genetic testing recommendations.

Comparison of the Clinical Features and Prognostic Value of Inflammation-Based Markers in Uterine Leiomyosarcoma

Aim: Inflammation-related markers are the factors affecting prognosis in many types of cancer. In this study, we aimed to investigate the relationship between inflammation-related markers, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and prognostic nutritional index (PNI) with prognosis of patients with uterine leiomyosarcoma (uLMS). Methods: Patients diagnosed with uLMS were reviewed retrospectively. NLR, PLR, SII, and PNI values were calculated at the diagnosis and before treatment. Totally 35 patients were included in the study. Results: Median overall survival (OS) in the low-NLR (

Implications of the Hippo Pathway Dysregulation in Uterine Leiomyosarcoma.

Uterine leiomyosarcomas (uLMS) are the most common mesenchymal tumors of the female genital tract. uLMS genetics encompass complex karyotypes with no specific molecular alterations. The Hippo pathway has been implicated in the pathogenesis of epithelioid hemangio-endotheliomas and endometrial sarcomas. Hippo pathway effectors are YAP1 and TAZ co-transcriptional factors. We studied Hippo pathway in a series of 32 uLMS patients and its association with clinicopathological parameters. Immunohistochemical analysis of YAP1 and TAZ proteins accompanied with fluorescent in situ hybridization study of YAP1 gene was performed in patient samples. Age, sex, tumor size, stage at the time of diagnosis and treatment have been analyzed. Overall survival (OS) was calculated from the time of diagnosis until death, loss of follow up or data cut-off. Hippo signaling was found to be dysregulated in 20 (62.5%) patients with uLMS. Regarding OS we detected a trend of Hippo deregulation, designating it as a positive prognostic factor. The Hippo pathway is implicated in uLMS oncogenesis, since nuclear expression of YAP1 was detected in 17 (53.1%) of the 32 patients with immunohistochemistry and YAP1 amplification was found in 8 (25%) patients.

Molecular genetics and research progress of uterine leiomyosarcoma.

Uterine leiomyosarcoma (uLMS) is a type of malignant soft-tissue tumor, which is developed from myometrium in the female reproductive system. This disease is difficult to be distinguished from benign uterine leiomyoma in the early stages, but it progresses aggressively and relentlessly. Hence, uLMS has a dismal prognosis and high rates of both misdiagnosis and missed diagnosis. Unfortunately, current studies of uLMS pathogenesis and disease biology are inadequate. uLMS disease models are also very limited, hindering the development of effective therapeutics. In this review, we focus on the pathological molecular biology of uLMS, and systematically review the molecular genetic features, epigenetic variants, experimental models, and clinical research progress of uLMS. We further discuss the development direction and potential needs of uLMS in the fields of tumor evolution, tumor microenvironment, and tumor therapy, with the aim of providing a better understanding of the pathobiological mechanism of uLMS and providing a reference for the development of potential diagnostic and therapeutic strategies.