Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.763
Filtrar
2.
J Cancer Res Clin Oncol ; 150(3): 134, 2024 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-38493445

RESUMO

PURPOSE: The CD47 molecule, often referred to as the "do not eat me" signal, is frequently overexpressed in tumor cells. This signaling pathway limits phagocytosis by macrophages. Our objective was to determine CD47 abundance in various soft tissue sarcomas (STS) to investigate whether it could serve as a potential evasion mechanism for tumor cells. Additionally, we aimed to assess the prognostic value of CD47 expression by examining its association with different clinicopathological factors. This study aimed to elucidate the significance of CD47 in the context of emerging anti-tumor targeting approaches. METHODS: In this retrospective study, formalin-fixed paraffine-embedded (FFPE) tumor tissues of 55 treatment-naïve patients were evaluated by immunohistochemistry for the abundance of CD47 molecule on tumor cells. The categorization of CD47 positivity was as follows: 0 (no staining of tumor cells), 1 + (less than 1/3 of tumor area positive), 2 + (between 1/3 and 2/3 of tumor area positive), and 3 + (more than 2/3 of tumor area positive for CD47). Next, we compared CD47 abundance between different tumor grades (G1-3). We used Kaplan-Meier survival curves with log-rank test to analyze the differences in survival between patients with different CD47 expression. Moreover, we performed Cox proportional hazards regression model to evaluate the clinical significance of CD47. RESULTS: CD47 is widely prevalent across distinct STS subtypes. More than 80% of high grade undifferentiated pleiomorphic sarcoma (UPS), 70% of myxofibrosarcoma (MFS) and more than 60% of liposarcoma (LPS) samples displayed a pattern of moderate-to-diffuse positivity. This phenomenon remains consistent regardless of the tumor grade. However, there was a tendency for higher CD47 expression levels in the G3 group compared to the combined G1 + G2 groups when all LPS, MFS, and UPS were analyzed together. No significant associations were observed between CD47 abundance, death, and metastatic status. Additionally, high CD47 expression was associated with a statistically significant increase in progression-free survival in the studied cohort of patients. CONCLUSION: This study highlights the potential of the CD47 molecule as a promising immunotherapeutic target in STS, particularly given its elevated expression levels in diverse sarcoma types. Our data showed a notable trend linking CD47 expression to tumor grade, while also suggesting an interesting correlation between enhanced abundance of CD47 expression and a reduced hazard risk of disease progression. Although these findings shed light on different roles of CD47 in STS, further research is crucial to assess its potential in clinical settings.


Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Humanos , Adulto , Antígeno CD47/metabolismo , Estudos Retrospectivos , Lipopolissacarídeos , Sarcoma/terapia , Macrófagos/patologia , Neoplasias de Tecidos Moles/patologia , Prognóstico
3.
J Cancer Res Clin Oncol ; 150(3): 112, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38436779

RESUMO

PURPOSE: CIC-rearranged sarcomas represent a type of undifferentiated small round cell sarcoma (USRCS) characterized by poor survival, rapid development of chemotherapy resistance, and high rates of metastasis. We aim to contribute to the growing body of knowledge regarding diagnosis, treatment, clinical course, and outcomes for these patients. METHODS: This case series investigates the clinical courses of ten patients with CIC-rearranged sarcoma treated at the Johns Hopkins Hospital from July 2014 through January 2024. Clinical data were retrospectively extracted from electronic medical records. RESULTS: Patients ranged from 10 to 67 years of age at diagnosis, with seven patients presenting with localized disease and three with metastatic disease. Tumors originated from soft tissues of various anatomic locations. Mean overall survival (OS) was 22.1 months (10.6-52.2), and mean progression-free survival (PFS) was 16.7 months (5.3-52.2). Seven patients received intensive systemic therapy with an Ewing sarcoma-directed regimen or a soft tissue sarcoma-directed regimen. Three patients experienced prolonged disease-free survival without systemic treatment. CONCLUSION: Most patients in this case series demonstrated aggressive clinical courses consistent with those previously described in the literature, although we note a spectrum of clinical outcomes not previously reported. The diversity of clinical courses underscores the need for an improved understanding of individual tumor biology to enhance clinical decision-making and patient prognosis. Despite its limitations, this article broadens the spectrum of reported clinical outcomes, providing a valuable addition to the published literature on this rare cancer.


Assuntos
Sarcoma de Ewing , Sarcoma , Humanos , Tomada de Decisão Clínica , Hospitais , Estudos Retrospectivos , Sarcoma/genética , Sarcoma/terapia , Sarcoma de Ewing/genética , Sarcoma de Ewing/terapia
4.
Mol Cancer ; 23(1): 38, 2024 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378555

RESUMO

Most soft-tissue sarcomas (STS) exhibit an immunosuppressive tumor microenvironment (TME), leading to resistance against immune checkpoint inhibitors (ICIs) and limited therapeutic response. Preclinical data suggest that oncolytic viral therapy can remodel the TME, facilitating T cell accumulation and enhancing the immunogenicity of these tumors.We conducted the METROMAJX, a phase II clinical trial, to investigate the combination of JX-594, an oncolytic vaccinia virus engineered for selective tumor cell replication, with metronomic cyclophosphamide and the PD-L1 inhibitor avelumab in patients with advanced, 'cold' STS, characterized by an absence of tertiary lymphoid structures. The trial employed a two-stage Simon design. JX-594 was administered intratumorally at a dose of 1.109 pfu every 2 weeks for up to 4 intra-tumoral administrations. Cyclophosphamide was given orally at 50 mg twice daily in a week-on, week-off schedule, and avelumab was administered at 10 mg/kg biweekly. The primary endpoint was the 6-month non-progression rate.Fifteen patients were enrolled, with the most frequent toxicities being grade 1 fatigue and fever. Fourteen patients were assessable for efficacy analysis. At 6 months, only one patient remained progression-free, indicating that the trial did not meet the first stage endpoint of Simon's design. Analysis of sequential tissue biopsies and plasma samples revealed an increase in CD8 density and upregulation of immune-related protein biomarkers, including CXCL10.Intra-tumoral administration of JX-594 in combination with cyclophosphamide and avelumab is safe and capable of modulating the TME in cold STS. However, the limited efficacy observed warrants further research to define the therapeutic potential of oncolytic viruses, particularly in relation to specific histological subtypes of STS.


Assuntos
Anticorpos Monoclonais Humanizados , Terapia Viral Oncolítica , Vírus Oncolíticos , Sarcoma , Humanos , Microambiente Tumoral , Terapia Viral Oncolítica/efeitos adversos , Vírus Oncolíticos/genética , Vírus Oncolíticos/metabolismo , Sarcoma/terapia , Ciclofosfamida/uso terapêutico , Ciclofosfamida/metabolismo
5.
BMJ Case Rep ; 17(2)2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38388202

RESUMO

Primary soft tissue sarcomas of the breast are rare aggressive neoplasms. These often are misdiagnosed with other more common neoplasms like fibroepithelial malignancies, namely phyllodes tumour and metaplastic carcinoma. Being uncommon, chances of being misdiagnosed are higher leading to early mortality. A multidisciplinary team incorporating surgery, pathology, chemotherapy and radiotherapy is required to formulate an approach to primary soft tissue sarcoma. Generally, these tumours may show single or dual phenotype; we present one rare case report showing multiphenotypic differentiation.


Assuntos
Neoplasias da Mama , Sarcoma , Neoplasias de Tecidos Moles , Feminino , Humanos , Mama/patologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Sarcoma/diagnóstico , Sarcoma/patologia , Sarcoma/terapia , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/terapia , Terapia Combinada , Equipe de Assistência ao Paciente
6.
BMC Med Educ ; 24(1): 138, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38350994

RESUMO

INTRODUCTION: Typically, oncology is not a structured part of the curriculum in Brazilian medical schools. Furthermore, sarcomas, which are uncommon tumors, are seldom covered in depth. A lack of comprehensive education on sarcomas might result in medical professionals being ill-equipped to care for patients with this condition. OBJECTIVES: To assess medical students' understanding and awareness of sarcomas and the specific principles related to these tumors. MATERIALS AND METHODS: A quantitative, cross-sectional study was conducted using a questionnaire, applied to medical students, focusing on the epidemiology, pathophysiology, and treatments of bone and soft tissue sarcomas. In all tests, the significance level adopted was 5%. The SPSS version 25.0 software was used. RESULTS: Of the 825 questionnaires distributed, 325 were returned. Educational sessions on sarcomas did not appear to significantly improve the student's knowledge. Only 29.5% of students identified the lack of pain as an indicator of potential malignancy in soft tissue sarcomas, while 73.8% correctly recognized pain as a symptom of bone sarcomas. Limb amputation as the optimal surgical method for patient recovery was incorrectly reported by 39.1% of the sample. CONCLUSION: A great part of the surveyed population does not have adequate knowledge about the basic concepts associated with limb sarcomas. The minority of them are satisfied with the knowledge gained during their medical education about these tumors. Inadequate medical academic training may initially lead to the wrong clinical management of patients with bone and soft tissue tumor lesions. An educational effort is needed to enhance oncology education for medical students, especially concerning sarcomas.


Assuntos
Sarcoma , Estudantes de Medicina , Humanos , Estudos Transversais , Sarcoma/diagnóstico , Sarcoma/epidemiologia , Sarcoma/terapia , Currículo , Dor
7.
PLoS One ; 19(2): e0298292, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38377118

RESUMO

Bone and soft-tissue sarcomas are rare malignancies with histological diversity and tumor heterogeneity, leading to the lack of a common molecular target. Telomerase is a key enzyme for keeping the telomere length and human telomerase reverse transcriptase (hTERT) expression is often activated in most human cancers, including bone and soft-tissue sarcomas. For targeting of telomerase-positive tumor cells, we developed OBP-301, a telomerase-specific replication-competent oncolytic adenovirus, in which the hTERT promoter regulates adenoviral E1 gene for tumor-specific viral replication. In this study, we present the diagnostic potential of green fluorescent protein (GFP)-expressing oncolytic adenovirus OBP-401 for assessing virotherapy sensitivity using bone and soft-tissue sarcomas. OBP-401-mediated GFP expression was significantly associated with the therapeutic efficacy of OBP-401 in human bone and soft-tissue sarcomas. In the tumor specimens from 68 patients, malignant and intermediate tumors demonstrated significantly higher expression levels of coxsackie and adenovirus receptor (CAR) and hTERT than benign tumors. OBP-401-mediated GFP expression was significantly increased in malignant and intermediate tumors with high expression levels of CAR and hTERT between 24 and 48 h after infection. Our results suggest that the OBP-401-based GFP expression system is a useful tool for predicting the therapeutic efficacy of oncolytic virotherapy on bone and soft-tissue sarcomas.


Assuntos
Infecções por Adenoviridae , Terapia Viral Oncolítica , Sarcoma , Neoplasias de Tecidos Moles , Telomerase , Humanos , Adenoviridae/fisiologia , Telomerase/genética , Telomerase/metabolismo , Fluorescência , Terapia Viral Oncolítica/métodos , Sarcoma/terapia , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Linhagem Celular Tumoral
8.
Medicine (Baltimore) ; 103(8): e37194, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38394547

RESUMO

RATIONALE: Pulmonary artery sarcoma (PAS) is a rare malignant tumor primarily originating from the pulmonary artery's intima or subintima. Approximately one-third of cases are classified as undifferentiated type. Its clinical manifestations lack specificity, dyspnea is the main symptom but can also present with chest pain, cough, hemoptysis, and other discomforts, making it prone to misdiagnosis as pulmonary embolism (PE). PATIENT CONCERNS: A 50-year-old woman was admitted to the hospital with "dyspnea for more than 3 months, aggravated for 2 days," and computed tomography pulmonary angiography suggesting "bilateral multiple pulmonary embolisms." DIAGNOSES: The patient was initially misdiagnosed as PE, and was later definitively diagnosed as undifferentiated pleomorphic sarcoma of the pulmonary artery by pathologic biopsy. INTERVENTIONS AND OUTCOMES: The patient was initially treated with anticoagulant therapy, but her dyspnea was not relieved. After that, she underwent positron emission computed tomography (PET-CT) and other investigations, which suggested the possibility of PAS, and then she underwent pulmonary endarterectomy to remove the lesion, which relieved her symptoms and was advised to seek further medical attention from the Department of Oncology and Department of Radiotherapy. LESSONS: PAS can be easily misdiagnosed as PE. If a diagnosis of PE is made, but anticoagulation or even thrombolytic therapy proves ineffective, and there is no presence of PE causative factors such as deep vein thrombosis in the lower extremities, or D-dimer levels are not high, one should be cautious and consider the possibility of PAS.


Assuntos
Hipertensão Pulmonar , Neoplasias Pulmonares , Embolia Pulmonar , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Feminino , Pessoa de Meia-Idade , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Hipertensão Pulmonar/complicações , Embolia Pulmonar/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias de Tecidos Moles/patologia , Dispneia/etiologia , Dispneia/patologia , Sarcoma/diagnóstico , Sarcoma/terapia , Sarcoma/complicações
10.
Gynecol Obstet Invest ; 89(2): 73-86, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38382486

RESUMO

BACKGROUND: Uterine fibroids are benign monoclonal tumors originating from the smooth muscle cells of the myometrium, constituting the most prevalent pathology within the female genital tract. Uterine sarcomas, although rare, still represent a diagnostic challenge and should be managed in centers with adequate expertise in gynecological oncology. OBJECTIVES: This article is aimed to summarize and discuss cutting-edge elements about the diagnosis and management of uterine fibroids and sarcomas. METHODS: This paper is a report of the lectures presented in an expert meeting about uterine fibroids and sarcomas held in Palermo in February 2023. OUTCOME: Overall, the combination of novel molecular pathways may help combine biomarkers and expert ultrasound for the differential diagnosis of uterine fibroids and sarcomas. On the one hand, molecular and cellular maps of uterine fibroids and matched myometrium may enhance our understanding of tumor development compared to histologic analysis and whole tissue transcriptomics, and support the development of minimally invasive treatment strategies; on the other hand, ultrasound imaging allows in most of the cases a proper mapping the fibroids and to differentiate between benign and malignant lesions, which need appropriate management. CONCLUSIONS AND OUTLOOK: The choice of uterine fibroid management, including pharmacological approaches, surgical treatment, or other strategies, such as high-intensity focused ultrasound (HIFU), should be carefully considered, taking into account the characteristics of the patient and reproductive prognosis.


Assuntos
Ablação por Ultrassom Focalizado de Alta Intensidade , Leiomioma , Sarcoma , Miomectomia Uterina , Neoplasias Uterinas , Feminino , Humanos , Resultado do Tratamento , Leiomioma/diagnóstico , Leiomioma/terapia , Leiomioma/patologia , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/terapia , Neoplasias Uterinas/patologia , Prognóstico , Sarcoma/diagnóstico , Sarcoma/terapia , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos
11.
J Cancer Res Clin Oncol ; 150(3): 108, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38421462

RESUMO

PURPOSE: This review primarily aims to review the epidemiology, clinical characteristics, imaging, pathology, immunohistochemistry, diagnosis, differential diagnosis, treatment, and prognosis of Primary pulmonary myxoid sarcoma (PPMS) with EWS RNA binding protein 1::cAMP response element binding protein 1 (EWSR1::CREB1) fusion. It provides reference for the diagnosis and treatment of this disease. METHODS: Retrospectively collected the literature about PPMS with EWSR1::CREB1 fusion, its clinical, radiology, histology, molecular characteristics and current treatment strategies were collated and analyzed. This review provides a detailed differential diagnosis of the disease. RESULTS: PPMS is an exceptionally rare, low-grade malignant tumor of the lung. This tumor commonly infiltrates lung tissue and develops within bronchial passages. It is identified by a genetic rearrangement involving the EWSR1 gene and a distinct chromosomal translocation t(2; 22)(q33; q12). Variants include EWSR1::CREB1 fusion and EWS RNA binding protein 1::activating transcription factors (EWSR1::ATF1) fusion. PPMS with EWSR1::CREB1 fusion is more prevalent among middle-aged individuals and affects both sexes almost equally. Clinical symptoms are relatively non-specific, primarily including cough, hemoptysis, and weight loss. Most patients undergo surgery and experience a favorable prognosis. Further research is required to validate the effectiveness of alternative treatments for PPMS with EWSR1::CREB1 fusion. CONCLUSION: EWSR1 rearrangement and EWSR1::CREB1 fusion are crucial genetic features of PPMS and serve as important diagnostic markers. Immunohistochemically, PPMS tests positive for EMA. In terms of treatment, surgery has been the primary approach in recent years. Therefore, the efficacy of other treatments still requires further investigation.


Assuntos
Aberrações Cromossômicas , Sarcoma , Feminino , Masculino , Pessoa de Meia-Idade , Humanos , Proteína EWS de Ligação a RNA/genética , Estudos Retrospectivos , Diagnóstico Diferencial , Sarcoma/diagnóstico , Sarcoma/genética , Sarcoma/terapia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética
12.
BMC Cancer ; 24(1): 215, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38360621

RESUMO

BACKGROUND: Genitourinary sarcomas are rare in adults and few large-scale studies on adult genitourinary sarcoma are reported. We aimed to elucidate the clinical characteristics, survival outcomes, and prognostic factors for overall survival of adult genitourinary sarcoma in Japan. METHODS: A hospital-based cancer registry data in Japan was used to identify and enroll patients diagnosed with genitourinary sarcoma in 2013. The datasets were registered from 121 institutions. RESULTS: A total of 116 men and 39 women were included, with a median age of 66 years. The most common primary site was the kidney in 47 patients, followed by the paratestis in 36 patients. The most common histological type was liposarcoma in 54 patients, followed by leiomyosarcoma in 25 patients. The 5-year overall survival rates were 57.6%. On univariate analysis, male gender, paratestis as primary organ, and histological subtype of liposarcoma were predictive of favorable survival while primary kidney, bladder, or prostate gland location were predictive of unfavorable survival. On multivariate analysis, primary paratestis was an independent predictor of favorable survival while primary kidney, bladder, or prostate gland were independent predictors of unfavorable survival. CONCLUSIONS: This is the first report showing the clinical characteristics and survival outcomes of adult genitourinary sarcoma in Japan using a real-world large cohort database.


Assuntos
Lipossarcoma , Sarcoma , Adulto , Humanos , Masculino , Feminino , Idoso , Japão/epidemiologia , Dados de Saúde Coletados Rotineiramente , Sarcoma/epidemiologia , Sarcoma/terapia , Lipossarcoma/patologia , Hospitais , Estudos Retrospectivos , Prognóstico
13.
J Clin Oncol ; 42(8): 898-906, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38232337

RESUMO

PURPOSE: A randomized trial was conducted to compare neoadjuvant standard (S) anthracycline + ifosfamide (AI) regimen with histology-tailored (HT) regimen in selected localized high-risk soft tissue sarcoma (STS). The results of the trial demonstrated the superiority of S in all STS histologies except for high-grade myxoid liposarcoma (HG-MLPS) where S and HT appeared to be equivalent. To further evaluate the noninferiority of HT compared with S, the HG-MLPS cohort was expanded. PATIENTS AND METHODS: Patients had localized high-grade (cellular component >5%; size ≥5 cm; deeply seated) MLPS of extremities or trunk wall. The primary end point was disease-free survival (DFS). The secondary end point was overall survival (OS). The trial used a noninferiority Bayesian design, wherein HT would be considered not inferior to S if the posterior probability of the true hazard ratio (HR) being >1.25 was <5%. RESULTS: From May 2011 to June 2020, 101 patients with HG-MLPS were randomly assigned, 45 to the HT arm and 56 to the S arm. The median follow-up was 66 months (IQR, 37-89). Median size was 107 mm (IQR, 84-143), 106 mm (IQR, 75-135) in the HT arm and 108 mm (IQR, 86-150) in the S arm. At 60 months, the DFS and OS probabilities were 0.86 and 0.73 (HR, 0.60 [95% CI, 0.24 to 1.46]; log-rank P = .26 for DFS) and 0.88 and 0.90 (HR, 1.20 [95% CI, 0.37 to 3.93]; log-rank P = .77 for OS) in the HT and S arms, respectively. The posterior probability of HR being >1.25 for DFS met the Bayesian monitoring cutoff of <5% (4.93%). This result confirmed the noninferiority of trabectedin to AI suggested in the original study cohort. CONCLUSION: Trabectedin may be an alternative to standard AI in HG-MLPS of the extremities or trunk when neoadjuvant treatment is a consideration.


Assuntos
Lipossarcoma Mixoide , Sarcoma , Neoplasias de Tecidos Moles , Adulto , Humanos , Terapia Neoadjuvante , Lipossarcoma Mixoide/tratamento farmacológico , Trabectedina/uso terapêutico , Polônia , Teorema de Bayes , Ifosfamida/uso terapêutico , Sarcoma/terapia , Neoplasias de Tecidos Moles/terapia , Antibióticos Antineoplásicos/uso terapêutico , Antraciclinas/uso terapêutico , Itália
14.
Eur J Med Res ; 29(1): 45, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38212774

RESUMO

There are more than 170 subtypes of sarcomas (SARC), which pose a challenge for diagnosis and patient management. Relatively simple or complex karyotypes play an indispensable role in the early diagnosis and effective treatment of SARC. The genes related to absorption, distribution, metabolism, and excretion (ADME) of a drug can serve as prognostic biomarkers of cancer and potential drug targets. In this study, a risk score signature was created. The SARC cohort was downloaded from The Cancer Genome Atlas (TCGA) database, and divided into high-risk group and low-risk group according to the median value of risk score. Compared with high-risk group, low-risk group has a longer survival time, which is also verified in osteosarcoma cohort from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. In addition, the relationship between the signature and immunophenotypes, including status of immune cell infiltration and immune checkpoint expression, was explored. Then, we found that high-risk group is in immunosuppressive status. Finally, we verified that PPARD played a role as a carcinogen in osteosarcoma, which provided a direction for targeted treatment of osteosarcoma in the future. Generally speaking, the signature can not only help clinicians predict the prognosis of patients with SARC, but also provide a theoretical basis for developing more effective targeted drugs in the future.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Prognóstico , Sarcoma/genética , Sarcoma/terapia , Osteossarcoma/genética , Osteossarcoma/terapia , Imunoterapia
16.
Nat Commun ; 15(1): 51, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38168093

RESUMO

Linking clinical multi-omics with mechanistic studies may improve the understanding of rare cancers. We leverage two precision oncology programs to investigate rhabdomyosarcoma with FUS/EWSR1-TFCP2 fusions, an orphan malignancy without effective therapies. All tumors exhibit outlier ALK expression, partly accompanied by intragenic deletions and aberrant splicing resulting in ALK variants that are oncogenic and sensitive to ALK inhibitors. Additionally, recurrent CKDN2A/MTAP co-deletions provide a rationale for PRMT5-targeted therapies. Functional studies show that FUS-TFCP2 blocks myogenic differentiation, induces transcription of ALK and truncated TERT, and inhibits DNA repair. Unlike other fusion-driven sarcomas, TFCP2-rearranged tumors exhibit genomic instability and signs of defective homologous recombination. DNA methylation profiling demonstrates a close relationship with undifferentiated sarcomas. In two patients, sarcoma was preceded by benign lesions carrying FUS-TFCP2, indicating stepwise sarcomagenesis. This study illustrates the potential of linking precision oncology with preclinical research to gain insight into the classification, pathogenesis, and therapeutic vulnerabilities of rare cancers.


Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Humanos , Multiômica , Medicina de Precisão , Fatores de Transcrição/genética , Sarcoma/genética , Sarcoma/terapia , Sarcoma/diagnóstico , Proteína EWS de Ligação a RNA/genética , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/terapia , Receptores Proteína Tirosina Quinases , Biomarcadores Tumorais/genética , Proteínas de Fusão Oncogênica/genética , Proteína-Arginina N-Metiltransferases , Proteínas de Ligação a DNA/genética
17.
J Am Acad Orthop Surg ; 32(3): e115-e124, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37852242

RESUMO

With nearly 15,000 new cases of soft-tissue sarcoma (STS) in the United States each year, early diagnosis and therapeutic management is imperative for successful patient outcomes. Primary STS is conventionally treated with a combination of wide-margin resection, neoadjuvant or adjuvant radiation therapy, and, in specific cases, adjuvant chemotherapy. However, in situations of complex disease presentation, guidelines for treatment are less clearly outlined. Limited metastatic disease, local recurrence, fungating STSs, and unplanned or incomplete resections of STSs present unique challenges for the multidisciplinary care team. The management of complex STS clinical scenarios usually involves limb-salvage resection or amputation as well as some combination of radiation therapy and/or ablative interventional radiology techniques. As a result, a multidisciplinary team approach is essential for treating patients in these challenging scenarios, with a recent focus on the integration of plastic and reconstructive surgery into the treatment algorithm.


Assuntos
Procedimentos de Cirurgia Plástica , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Sarcoma/terapia , Sarcoma/tratamento farmacológico , Salvamento de Membro , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/terapia , Neoplasias de Tecidos Moles/patologia , Amputação Cirúrgica , Estudos Retrospectivos
18.
Mod Pathol ; 37(2): 100400, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38043789

RESUMO

Soft tissue sarcomas harboring EWSR1::PATZ1 are a recently recognized entity with variable morphology and a heterogeneous immunohistochemical profile. We studied 17 such tumors. The tumors occurred in 12 men and 5 women (median age, 50 years; range, 15-71 years), involved the thoracoabdominal soft tissues (14 cases; 82%), lower extremities (2 cases; 12%), and tongue (1 case; 6%), and ranged from 0.7 to 11.3 cm (median, 4.7 cm). All but 1 patient received complete surgical resection; 7 were also treated with neoadjuvant chemo/radiotherapy. All cases showed typical features of EWSR1::PATZ1 sarcoma, including uniform round to spindled cells, fibromyxoid matrix, fibrous bands, hyalinized vessels, and pseudoalveolar/microcystic spaces. Unusual features, seen in a subset of cases, included degenerative-appearing nuclear atypia, epithelioid cytomorphology, mature fat, abundant rhabdomyoblasts, high mitotic activity, and foci with increased cellularity and nuclear atypia. Positive immunohistochemical results were desmin (16/17, 94%), MyoD1 (13/14, 93%), myogenin (6/14, 43%), GFAP (10/10, 100%), S100 protein (15/17, 88%), SOX10 (7/13, 54%), keratin (10/17, 59%), CD99 (4/11, 36%), H3K27me3 (retained expression 9/9, 100%), p16 (absent expression 1/4, 25%), and p53 (wild type 3/3, 100%). Fusion events included EWSR1 exon 8::PATZ1 exon 1 (14/17, 82%), EWSR1 exon 9::PATZ1 exon 1 (2/17, 12%), and EWSR1 exon 7::PATZ1 exon 1 (1/17, 6%). No evaluated tumor had alterations of CDKN2A/B and/or TP53, or MDM2 amplification. Clinical follow-up (16 patients: median, 13.5 months; range, 1-77 months) showed distant metastases in 3 patients (1/3 at time of presentation) and no local recurrences. At the time of last follow-up, 14 patients were disease free, 1 was alive with disease, 1 was dead of disease (at 13 months), and 1 had an indeterminant pulmonary nodule. We conclude that the morphologic spectrum of EWSR1::PATZ1 is broader than has been previously appreciated. Although more long-term follow-up is needed, the prognosis of these very rare sarcomas may be more favorable than previously reported.


Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Sarcoma/genética , Sarcoma/terapia , Sarcoma/patologia , Fatores de Transcrição , Proteína EWS de Ligação a RNA/genética , Proteínas S100 , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/terapia , Neoplasias de Tecidos Moles/patologia , Prognóstico , Biomarcadores Tumorais/genética , Proteínas Repressoras/genética , Fatores de Transcrição Kruppel-Like
19.
Am J Clin Pathol ; 161(3): 256-263, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37921094

RESUMO

OBJECTIVES: Intimal sarcomas are rare, aggressive neoplasms that arise from large blood vessels. Characterization of the tumor immune microenvironment may suggest new treatment strategies. METHODS: Seventeen specimens from 7 patients were labeled by immunohistochemistry for programmed cell death 1 ligand 1 (PD-L1), CD45, CD8, CD4, FOXP3, CD20, CD68, and LAG3. The immune cell density was scored as a percentage of the tumor area (1+ [<5%], 2+ [5%-50%], 3+ [>50%]); PD-L1 expression was scored on tumor cells and on intratumoral immune cells. Immune marker density was quantified using image analysis software. RESULTS: All intimal sarcomas showed immune cell infiltration (41% were 1+, 53% were 2+, 6% were 3+). Tumor and immune cell PD-L1 labeling was seen in 35% and 76% of cases, respectively; PD-L1+ intimal sarcomas had higher CD45+, CD8+, FOXP3+, CD68+, and leukocyte activation gene 3 (LAG3)+ cell densities (P ≤ .01). Similarly, PD-L1 expression on immune cells correlated with higher densities of CD8+ and FOXP3+ cells (P < .04). Higher LAG3+ cell density correlated with higher CD68+ cell density and necrosis (P < .05). One patient with prolonged survival had the highest immune cell density and PD-L1 expression. CONCLUSIONS: These data show that intimal sarcomas have an active tumor microenvironment with an adaptive pattern of PD-L1 expression. Our results suggest that immunotherapy may be an effective treatment option.


Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Humanos , Antígeno B7-H1 , Sarcoma/terapia , Fatores de Transcrição Forkhead , Processamento de Imagem Assistida por Computador , Microambiente Tumoral
20.
Vet Comp Oncol ; 22(1): 12-21, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37918913

RESUMO

Due to the low frequency and the changes in diagnostic techniques and terminology during the last few years, only little clinical information is available on splenic stromal sarcoma (SSS). This multi-institutional study aimed at gathering clinical cases of SSS in dogs and investigates their clinical behaviour, as well as analyse possible clinicopathological prognostic factors, including the use of adjuvant therapy. Dogs with a histologically confirmed SSS that underwent splenectomy were retrospectively included. To be included in the study, either FFPE tissue blocks or multiple tissue sections had to be available for histopathologic and immunohistochemical revision. Clinical and pathological variables, along with adjuvant therapy data, were collected. Cumulative incidence of metastatic disease was analysed through univariate and bivariate analyses. The impact of adjuvant chemotherapy on metastasis incidence and survival was assessed, considering an estimated propensity score. A total of 32 dogs were included. Among them, 22 developed metastases with an incidence of 37.5%, 59.38%, and 65.94% at 6, 12, and 24 months, respectively. Univariate analysis identified mitotic count, total scoring, and necrosis as prognostic factors. In bivariate analysis, mitotic count remained prognostic. The administration of adjuvant chemotherapy did not have an impact on metastasis incidence or survival time. The study found that dogs with SSSs are at high risk of metastasis, although a small subgroup may experience longer survival after splenectomy. Mitotic count was the only variable having a reliable prognostic impact. Adjuvant chemotherapy did not appear to decrease the incidence of metastasis or prolong survival in these dogs.


Assuntos
Doenças do Cão , Sarcoma , Neoplasias de Tecidos Moles , Cães , Animais , Prognóstico , Estudos Retrospectivos , Doenças do Cão/diagnóstico , Doenças do Cão/cirurgia , Sarcoma/diagnóstico , Sarcoma/terapia , Sarcoma/veterinária , Baço/patologia , Neoplasias de Tecidos Moles/tratamento farmacológico , Neoplasias de Tecidos Moles/veterinária , Quimioterapia Adjuvante/veterinária
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...