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2.
Medicine (Baltimore) ; 103(23): e38393, 2024 Jun 07.
Article En | MEDLINE | ID: mdl-38847665

To explore the expression and prognostic value of UHRF1 gene in soft tissue sarcoma (STS) and its related molecular mechanism. The expression data and clinicopathological parameters of STS were downloaded from the Cancer Genome Atlas (TCGA). The expression level of UHRF1 in STS and adjacent tissues and its relationship with clinicopathological characteristics were analyzed. The expression level of UHRF1 in STS tissues was significantly higher than that in paracancerous tissues (P < .001), and the overall survival (OS) time of patients with high UHRF1 expression was significantly shorter than that of patients with low UHRF1 expression (P = .002). The expression of UHRF1 was correlated with tumor necrosis, histological type and metastasis, and the differences were statistically significant (P = .013; P = .001; P = .002). The area ratio under receiver operating characteristic (ROC) curve between STS tissue and adjacent tissue of UHRF1 expression was 0.994. Number of tumors (HR = 0.416, 95%CI = 0.260-0.666, P < .001), depth of tumor (HR = 2.888, 95%CI = 0.910-9.168, P = .033), metastasis (HR = 2.888, 95% CI = 1.762-4.732, P < .001), residual tumor (HR = 2.637, 95% CI = 1.721-4.038, P < .001) and UHRF1 expression (HR = 1.342, 95% CI = 1.105-1.630, P = .003) were significantly associated with OS, and high expression of UHRF1 (HR = 1.387, 95%CI = 1.008-1.907, P = .044) was an independent risk factor for the prognosis of STS patients. The results of the nomogram exhibited that UHRF1 expression level had a significant effect on the total score value. GSEA enrichment analysis suggested that UHRF1 was involved in 14 signaling pathways regulating mRNA spliceosome, cell cycle, P53 signaling pathway were identified. Single sample gene set enrichment analysis (ssGSEA) exhibited that the expression of UHRF1 in STS was positively correlated with the level of Th2 cell infiltration, and negatively correlated with plasmacytoid dendritic cells (pDC), natural killer cells (NK), Eosinophils, Mast cells, etc. UHRF1 expression is involved in the immune microenvironment of HCC and affects the occurrence and development of HCC. UHRF1 is highly expressed in STS tissues. It is involved in the regulation of multiple tumor-related signaling pathways and immune cell microenvironment, suggesting that UHRF1 may be a potential molecular marker for prognosis prediction and targeted therapy of STS patients.


Biomarkers, Tumor , CCAAT-Enhancer-Binding Proteins , Sarcoma , Ubiquitin-Protein Ligases , Humans , CCAAT-Enhancer-Binding Proteins/genetics , CCAAT-Enhancer-Binding Proteins/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolism , Sarcoma/genetics , Sarcoma/pathology , Sarcoma/mortality , Sarcoma/metabolism , Female , Prognosis , Male , Middle Aged , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , Adult , ROC Curve , Aged , Clinical Relevance
3.
Cancer Imaging ; 24(1): 59, 2024 May 08.
Article En | MEDLINE | ID: mdl-38720384

BACKGROUND: To develop a magnetic resonance imaging (MRI)-based radiomics signature for evaluating the risk of soft tissue sarcoma (STS) disease progression. METHODS: We retrospectively enrolled 335 patients with STS (training, validation, and The Cancer Imaging Archive sets, n = 168, n = 123, and n = 44, respectively) who underwent surgical resection. Regions of interest were manually delineated using two MRI sequences. Among 12 machine learning-predicted signatures, the best signature was selected, and its prediction score was inputted into Cox regression analysis to build the radiomics signature. A nomogram was created by combining the radiomics signature with a clinical model constructed using MRI and clinical features. Progression-free survival was analyzed in all patients. We assessed performance and clinical utility of the models with reference to the time-dependent receiver operating characteristic curve, area under the curve, concordance index, integrated Brier score, decision curve analysis. RESULTS: For the combined features subset, the minimum redundancy maximum relevance-least absolute shrinkage and selection operator regression algorithm + decision tree classifier had the best prediction performance. The radiomics signature based on the optimal machine learning-predicted signature, and built using Cox regression analysis, had greater prognostic capability and lower error than the nomogram and clinical model (concordance index, 0.758 and 0.812; area under the curve, 0.724 and 0.757; integrated Brier score, 0.080 and 0.143, in the validation and The Cancer Imaging Archive sets, respectively). The optimal cutoff was - 0.03 and cumulative risk rates were calculated. DATA CONCLUSION: To assess the risk of STS progression, the radiomics signature may have better prognostic power than a nomogram/clinical model.


Disease Progression , Magnetic Resonance Imaging , Nomograms , Sarcoma , Humans , Sarcoma/diagnostic imaging , Sarcoma/surgery , Sarcoma/pathology , Male , Female , Middle Aged , Retrospective Studies , Magnetic Resonance Imaging/methods , Adult , Aged , Machine Learning , Prognosis , Young Adult , Soft Tissue Neoplasms/diagnostic imaging , Soft Tissue Neoplasms/surgery , Soft Tissue Neoplasms/pathology , ROC Curve , Radiomics
4.
Front Endocrinol (Lausanne) ; 15: 1371910, 2024.
Article En | MEDLINE | ID: mdl-38803474

Background: This study represented the inaugural effort to develop predictive survival nomograms for metastatic soft tissue sarcoma (mSTS) patients in the era of immune checkpoint inhibitors. Method: From the Surveillance, Epidemiology, and End Results (SEER) program database, we extracted 3078 eligible patients with mSTS between 2016 and 2022. Kaplan-Meier survival analysis, univariate and multivariable Cox analyses, and univariate and multivariable logistic analyses were conducted. Subsequently, predictive nomograms were constructed. Clinical effectiveness was validated using the area under the curve (AUC), calibration curve, and decision curve analysis (DCA) methods. Results: We used the SEER database to include 3078 eligible patients with mSTS between 2016 and 2022. All the eligible patients were randomly allocated in a ratio of 6:4 and stratified into a training group (n = 1846) and a validation group (n = 1232). In the multivariate Cox analysis, age, race, marital status, pathological grade, histologic subtype, surgery, and chemotherapy were identified as independent prognostic factors. These factors were used to construct the nomogram to predict the 1-, 3-, and 5-year OS of mSTS patients. The C-index for the training cohort and the validation cohort was 0.722(95% confidence interval [CI]: 0.708-0.736), and 0.716(95% CI: 0.698-0.734), respectively. The calibration curves for 1-, 3-, and 5-year OS probability demonstrated excellent calibration between the predicted and the actual survival. The AUC values of the nomogram at 1-, 3-, and 5-year were 0.785, 0.767, and 0.757 in the training cohort, 0.773, 0.754, and 0.751 in the validation cohort, respectively. Furthermore, DCA indicated the favorable clinical utility of the nomogram in both cohorts. The risk stratification system was constructed using the established nomogram, which enhanced prediction accuracy, aided clinicians in identifying high-risk patients and informing treatment decisions. Conclusion: This study marked the inaugural effort in constructing predictive survival nomograms mSTS patients in the era of immune checkpoint inhibitors. The robustly constructed nomograms, alongside actual outcomes, offered valuable insights to inform follow-up management strategies.


Nomograms , SEER Program , Sarcoma , Humans , Sarcoma/mortality , Sarcoma/pathology , Sarcoma/therapy , Male , Female , Middle Aged , Prognosis , Aged , Adult , Survival Rate , Neoplasm Metastasis
5.
Radiat Oncol ; 19(1): 56, 2024 May 14.
Article En | MEDLINE | ID: mdl-38745333

BACKGROUND: Oncologic surgical resection is the standard of care for extremity and truncal soft tissue sarcoma (STS), often accompanied by the addition of pre- or postoperative radiation therapy (RT). Preoperative RT may decrease the risk of joint stiffness and fibrosis at the cost of higher rates of wound complications. Hypofractionated, preoperative RT has been shown to provide acceptable outcomes in prospective trials. Proton beam therapy (PBT) provides the means to decrease dose to surrounding organs at risk, such as the skin, bone, soft tissues, and adjacent joint(s), and has not yet been studied in patients with extremity and truncal sarcoma. METHODS: Our study titled "PROspective phase II trial of preoperative hypofractionated protoN therapy for extremity and Truncal soft tissue sarcOma (PRONTO)" is a non-randomized, prospective phase II trial evaluating the safety and efficacy of preoperative, hypofractionated PBT for patients with STS of the extremity and trunk planned for surgical resection. Adult patients with Eastern Cooperative Group Performance Status ≤ 2 with resectable extremity and truncal STS will be included, with the aim to accrue 40 patients. Treatment will consist of 30 Gy radiobiological equivalent of PBT in 5 fractions delivered every other day, followed by surgical resection 2-12 weeks later. The primary outcome is rate of major wound complications as defined according to the National Cancer Institute of Canada Sarcoma2 (NCIC-SR2) Multicenter Trial. Secondary objectives include rate of late grade ≥ 2 toxicity, local recurrence-free survival and distant metastasis-free survival at 1- and 2-years, functional outcomes, quality of life, and pathologic response. DISCUSSION: PRONTO represents the first trial evaluating the use of hypofractionated PBT for STS. We aim to prove the safety and efficacy of this approach and to compare our results to historical outcomes established by previous trials. Given the low number of proton centers and limited availability, the short course of PBT may provide the opportunity to treat patients who would otherwise be limited when treating with daily RT over several weeks. We hope that this trial will lead to increased referral patterns, offer benefits towards patient convenience and clinic workflow efficiency, and provide evidence supporting the use of PBT in this setting. TRIAL REGISTRATION: NCT05917301 (registered 23/6/2023).


Extremities , Proton Therapy , Radiation Dose Hypofractionation , Sarcoma , Humans , Proton Therapy/methods , Sarcoma/radiotherapy , Sarcoma/pathology , Prospective Studies , Adult , Female , Male , Soft Tissue Neoplasms/radiotherapy , Soft Tissue Neoplasms/pathology , Soft Tissue Neoplasms/surgery , Preoperative Care , Torso
6.
Cell Mol Life Sci ; 81(1): 219, 2024 May 17.
Article En | MEDLINE | ID: mdl-38758230

HMGA1 is a structural epigenetic chromatin factor that has been associated with tumor progression and drug resistance. Here, we reported the prognostic/predictive value of HMGA1 for trabectedin in advanced soft-tissue sarcoma (STS) and the effect of inhibiting HMGA1 or the mTOR downstream pathway in trabectedin activity. The prognostic/predictive value of HMGA1 expression was assessed in a cohort of 301 STS patients at mRNA (n = 133) and protein level (n = 272), by HTG EdgeSeq transcriptomics and immunohistochemistry, respectively. The effect of HMGA1 silencing on trabectedin activity and gene expression profiling was measured in leiomyosarcoma cells. The effect of combining mTOR inhibitors with trabectedin was assessed on cell viability in vitro studies, whereas in vivo studies tested the activity of this combination. HMGA1 mRNA and protein expression were significantly associated with worse progression-free survival of trabectedin and worse overall survival in STS. HMGA1 silencing sensitized leiomyosarcoma cells for trabectedin treatment, reducing the spheroid area and increasing cell death. The downregulation of HGMA1 significantly decreased the enrichment of some specific gene sets, including the PI3K/AKT/mTOR pathway. The inhibition of mTOR, sensitized leiomyosarcoma cultures for trabectedin treatment, increasing cell death. In in vivo studies, the combination of rapamycin with trabectedin downregulated HMGA1 expression and stabilized tumor growth of 3-methylcholantrene-induced sarcoma-like models. HMGA1 is an adverse prognostic factor for trabectedin treatment in advanced STS. HMGA1 silencing increases trabectedin efficacy, in part by modulating the mTOR signaling pathway. Trabectedin plus mTOR inhibitors are active in preclinical models of sarcoma, downregulating HMGA1 expression levels and stabilizing tumor growth.


HMGA1a Protein , Sarcoma , Trabectedin , Trabectedin/pharmacology , Humans , Sarcoma/drug therapy , Sarcoma/pathology , Sarcoma/genetics , Sarcoma/metabolism , HMGA1a Protein/metabolism , HMGA1a Protein/genetics , Animals , Cell Line, Tumor , Mice , Antineoplastic Agents, Alkylating/pharmacology , Antineoplastic Agents, Alkylating/therapeutic use , Drug Resistance, Neoplasm/genetics , Drug Resistance, Neoplasm/drug effects , TOR Serine-Threonine Kinases/metabolism , Gene Expression Regulation, Neoplastic/drug effects , Signal Transduction/drug effects , Prognosis , Female , Leiomyosarcoma/drug therapy , Leiomyosarcoma/pathology , Leiomyosarcoma/genetics , Leiomyosarcoma/metabolism , Xenograft Model Antitumor Assays
7.
Sci Rep ; 14(1): 10038, 2024 05 02.
Article En | MEDLINE | ID: mdl-38693188

To assess epidemiology, clinical presentation, treatment and overall survival of adult patients with renal sarcomas, the 2004-2016 SEER and NCDB databases were queried for adult patients diagnosed with renal sarcoma, calculating average annual age-adjusted incidence rates (AAIR) and average annual percentage change (AAPC) as well as overall survival (OS). In n = 1279 included renal sarcoma patients, AAIR remained constant over the study period (average 0.53 cases/1million; AAPC = 0.7, p = 0.6). Leiomyosarcoma (AAIR 0.14 cases/1 million) and malignant rhabdoid tumors (0.06 cases/1 million) were most common. Sarcoma histiotypes demonstrated considerable heterogeneity regarding demographic and cancer-related variables. Patients presented with advanced local extent (T3 33.3%; T4 14.2%) or distant metastases (29.1%) and commonly underwent surgical resection (81.6%). Longer OS was independently associated with younger age, female sex, lower comorbidity index, low T stage, negative surgical margins, absence of tumor necrosis or distant metastases and leiomyosarcoma histiotype (multivariable p < 0.05 each). Treatment efficacy varied according to sarcoma histiotype (interaction p < 0.001). Accounting for 0.25% of renal malignancies, renal sarcomas include 43 histiotypes with distinct epidemiology, clinical presentation, outcomes and sensitivity to systemic therapy, thereby reflecting soft-tissue sarcoma behavior. Renal sarcoma treatment patterns follow recommendations by renal cancer guidelines with surgical resection as the cornerstone of therapy.


Kidney Neoplasms , Sarcoma , Humans , Male , Female , Middle Aged , Sarcoma/epidemiology , Sarcoma/therapy , Sarcoma/mortality , Sarcoma/pathology , Kidney Neoplasms/epidemiology , Kidney Neoplasms/therapy , Kidney Neoplasms/pathology , Kidney Neoplasms/mortality , Aged , Adult , Treatment Outcome , Incidence , SEER Program , Aged, 80 and over
9.
Sci Rep ; 14(1): 12374, 2024 05 29.
Article En | MEDLINE | ID: mdl-38811642

Circulating tumor cells (CTCs) have gathered attention as a biomarker for carcinomas. However, CTCs in sarcomas have received little attention. In this work, we investigated cell surface proteins and antibody combinations for immunofluorescence detection of sarcoma CTCs. A microfluidic device that combines filtration and immunoaffinity using gangliosides 2 and cell surface vimentin (CSV) antibodies was employed to capture CTCs. For CTC detection, antibodies against cytokeratins 7 and 8 (CK), pan-cytokeratin (panCK), or a combination of panCK and CSV were used. Thirty-nine blood samples were collected from 21 patients of various sarcoma subtypes. In the independent samples study, samples were subjected to one of three antibody combination choices. Significant difference in CTC enumeration was found between CK and panCK + CSV, and between panCK and panCK + CSV. Upon stratification of CK+ samples, those of metastatic disease had a higher CTC number than those of localized disease. In the paired samples study involving cytokeratin-positive sarcoma subtypes, using panCK antibody detected more CTCs than CK. Similarly, for osteosarcoma, using panCK + CSV combination resulted in a higher CTC count than panCK. This study emphasized deliberate selection of cell surface proteins for sarcoma CTC detection and subtype stratification for studying cancers as heterogeneous as sarcomas.


Biomarkers, Tumor , Neoplastic Cells, Circulating , Sarcoma , Humans , Neoplastic Cells, Circulating/pathology , Neoplastic Cells, Circulating/metabolism , Sarcoma/pathology , Sarcoma/blood , Sarcoma/diagnosis , Sarcoma/metabolism , Biomarkers, Tumor/blood , Female , Male , Membrane Proteins/metabolism , Membrane Proteins/immunology , Keratins/immunology , Keratins/metabolism , Middle Aged , Adult , Vimentin/metabolism , Vimentin/immunology , Aged , Antibodies/immunology , Cell Line, Tumor
10.
J Stomatol Oral Maxillofac Surg ; 125(2): 101656, 2024 Apr.
Article En | MEDLINE | ID: mdl-38738551

Oral metastatic sarcomas (OMSs) occur only occasionally, and information about their characteristics is based on the restricted number of cases reported in the literature. This study aims to systematically review the English literature to recognize the clinicopathologic characteristics of OMSs. An electronic search was performed in PubMed Central and Scopus databases. The search included all the published articles (human case reports and case series) up till April 2023, with no time restrictions. OMSs were slightly more prevalent in males in their fifth to seventh decades of life. However, a high percentage of OMSs has been reported in the second decade of life. Lower extremities, breasts and uterus are the most common primary origin of metastatic sarcoma. Gingiva and mandible were common locations in the oral cavity for metastatic deposits. Generally, they demonstrated widespread affliction. The mean time interval between primary tumor detection and diagnosis of the oral metastasis was about 33.54 ± 36.19 months. Death was reported in 83 patients (67.48 %) with a mean survival rate of 7.98 ± 10.30 months. The most common microscopic tumor types were leiomyosarcoma (n = 21, 17 %), followed by angiosarcoma (n = 20, 16.26 %) and osteosarcoma (n = 18, 14.63 %). In conclusion, while oral metastases of sarcomas are not common, those should be considered in the differential diagnosis of the oral lesions. Although OMSs show a high occurrence in the 7th decade of the life, the average age of patients with oral involvement is lower than the overall metastatic lesions. OMSs may present as widespread disease with poor prognosis.


Mouth Neoplasms , Sarcoma , Humans , Mouth Neoplasms/pathology , Mouth Neoplasms/diagnosis , Mouth Neoplasms/epidemiology , Sarcoma/diagnosis , Sarcoma/pathology , Sarcoma/secondary , Sarcoma/epidemiology , Female , Male
11.
Surg Pathol Clin ; 17(2): 243-255, 2024 Jun.
Article En | MEDLINE | ID: mdl-38692808

Primary sarcoma of the lung and mediastinum is rare. The diagnosis requires careful exclusion of sarcomatoid carcinoma, sarcomatoid mesothelioma, and metastases from extra-thoracic sites. This review summarizes the key morphologic, immunohistochemical, and molecular characteristics of sarcomas that are encountered in the lung and mediastinum. The tumor types discussed are synovial sarcoma, well-differentiated/dedifferentiated liposarcoma, myxoid pleomorphic liposarcoma, intimal sarcoma of the pulmonary artery, inflammatory myofibroblastic tumor, epithelioid hemangioendothelioma, primary pulmonary myxoid sarcoma, malignant peripheral nerve sheath tumor, Ewing sarcoma, and CIC-rearranged sarcoma. Relevant differential diagnoses are also addressed.


Lung Neoplasms , Mediastinal Neoplasms , Sarcoma , Humans , Mediastinal Neoplasms/pathology , Mediastinal Neoplasms/diagnosis , Lung Neoplasms/pathology , Lung Neoplasms/diagnosis , Sarcoma/pathology , Sarcoma/diagnosis , Diagnosis, Differential , Biomarkers, Tumor
12.
Surg Pathol Clin ; 17(2): 257-270, 2024 Jun.
Article En | MEDLINE | ID: mdl-38692809

Spindle cell lesions of the pleura and pericardium are rare. Distinction from sarcomatoid mesothelioma, which has a range of morphologic patterns, can be difficult, but accurate diagnosis matters. This article provides practical guidance for the diagnosis of pleural spindle cell neoplasms, focusing on primary lesions.


Pericardium , Pleural Neoplasms , Humans , Pericardium/pathology , Pleural Neoplasms/pathology , Pleural Neoplasms/diagnosis , Diagnosis, Differential , Heart Neoplasms/pathology , Heart Neoplasms/diagnosis , Mesothelioma/pathology , Mesothelioma/diagnosis , Sarcoma/pathology , Sarcoma/diagnosis , Biomarkers, Tumor/analysis , Pleura/pathology
13.
J Int Med Res ; 52(5): 3000605241255504, 2024 May.
Article En | MEDLINE | ID: mdl-38759217

Retroperitoneal spindle cell neoplasms are diagnostically challenging. Malignant peripheral nerve sheath tumours (MPNSTs) can sometimes present as sporadic primary retroperitoneal tumours. MPNSTs are usually high-grade and highly aggressive tumours and are associated with a poor prognosis. Low-grade MPNSTs are very rarely described. This current case report describes a case of sporadic primary low-grade MPNST presenting as retroperitoneal spindle cell neoplasm. The diagnosis, imaging and immunohistopathological findings, as well as its successful surgical management, are presented.


Nerve Sheath Neoplasms , Retroperitoneal Neoplasms , Humans , Retroperitoneal Neoplasms/pathology , Retroperitoneal Neoplasms/diagnosis , Retroperitoneal Neoplasms/surgery , Retroperitoneal Neoplasms/diagnostic imaging , Nerve Sheath Neoplasms/pathology , Nerve Sheath Neoplasms/diagnosis , Nerve Sheath Neoplasms/surgery , Male , Middle Aged , Diagnosis, Differential , Neoplasm Grading , Sarcoma/diagnosis , Sarcoma/pathology , Sarcoma/surgery , Sarcoma/diagnostic imaging , Tomography, X-Ray Computed , Female
14.
Cancer Med ; 13(11): e7282, 2024 Jun.
Article En | MEDLINE | ID: mdl-38819113

AIMS: We endeavored to introduce a novel scoring system (Lumbar Functional Index, LFI) capable of evaluating lumbar function in pelvic bone sarcoma patients who underwent surgical resection and spinal pelvic fixation, while simultaneously identifying the incidence, outcomes, and risk factors of lumbar function impairment among these populations. PATIENTS AND METHODS: A cohort of 304 primary bone sarcoma patients were recruited. The LFI was created based on the Oswestry Dysfunction Index (ODI) and Japanese Orthopaedic Association (JOA) scores. Lumbar function impairment was defined as LFI score ≥ 18 points, which was identified as high LFI. Demographic data, clinical characteristics, and oncological outcomes were analyzed. RESULTS: The cohort included chondrosarcoma (39.8%), osteosarcoma (29.9%), Ewing sarcoma (8.6%), bone-derived undifferentiated pleomorphic sarcoma (7.2%), giant cell tumor of bone (7.2%), chordoma (2.3%), and other bone sarcomas (5.0%). The LFI score exhibited significant negative correlation with common scoring systems of bone sarcoma. The incidence of high LFI was 23.0%. Patients with high LFI demonstrated a higher prevalence of type I + II + III + IV pelvic tumor, more sacrificed nerve roots and bilateral lumbar spine fixation during surgery, while lower percentage of R0 resection and local control of pelvic tumor. Decreased median overall survival (30 vs. 52 months, p < 0.001) and recurrence-free survival (14 vs. 24 months, p < 0.001) time were observed in these patients. Type I + II + III + IV pelvic tumor and sacrificed nerve roots≥2 were identified as risk factors for high LFI, while R0 resection and local control were identified as protective factors. CONCLUSION: The LFI scoring system exhibited a significant negative correlation to current scoring systems. High LFI patients had worse prognosis and distinct characteristics. The risk factors of high LFI included type I + II + III + IV pelvic tumor and sacrificed nerve roots≥2, and the protective factors included R0 resection and local control.


Bone Neoplasms , Pelvic Bones , Humans , Male , Female , Bone Neoplasms/surgery , Bone Neoplasms/pathology , Adult , Middle Aged , Adolescent , Young Adult , Pelvic Bones/surgery , Pelvic Bones/pathology , Sarcoma/surgery , Sarcoma/pathology , Lumbar Vertebrae/surgery , Lumbar Vertebrae/pathology , Aged , Child , Risk Factors , Osteosarcoma/surgery , Osteosarcoma/mortality , Lumbosacral Region/surgery
15.
Sci Rep ; 14(1): 12516, 2024 05 31.
Article En | MEDLINE | ID: mdl-38822058

Pleomorphic dermal sarcomas are infrequent neoplastic skin tumors, manifesting in regions of the skin exposed to ultraviolet radiation. Diagnosing the entity can be challenging and therapeutic options are limited. We analyzed 20 samples of normal healthy skin tissue (SNT), 27 malignant melanomas (MM), 20 cutaneous squamous cell carcinomas (cSCC), and 24 pleomorphic dermal sarcomas (PDS) using mass spectrometry. We explored a potential cell of origin in PDS and validated our findings using publicly available single-cell sequencing data. By correlating tumor purity (TP), inferred by both RNA- and DNA-sequencing, to protein abundance, we found that fibroblasts shared most of the proteins correlating to TP. This observation could also be made using publicly available SNT single cell sequencing data. Moreover, we studied relevant pathways of receptor/ligand (R/L) interactions. Analysis of R/L interactions revealed distinct pathways in cSCC, MM and PDS, with a prominent role of PDGFRB-PDGFD R/L interactions and upregulation of PI3K/AKT signaling pathway. By studying differentially expressed proteins between cSCC and PDS, markers such as MAP1B could differentiate between these two entities. To this end, we studied proteins associated with immunosuppression in PDS, uncovering that immunologically cold PDS cases shared a "negative regulation of interferon-gamma signaling" according to overrepresentation analysis.


Melanoma , Proteomics , Skin Neoplasms , Humans , Skin Neoplasms/metabolism , Skin Neoplasms/pathology , Skin Neoplasms/immunology , Proteomics/methods , Melanoma/metabolism , Melanoma/pathology , Melanoma/immunology , Fibroblasts/metabolism , Sarcoma/metabolism , Sarcoma/pathology , Sarcoma/immunology , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/immunology , Female , Male , Melanoma, Cutaneous Malignant , Immune Evasion , Middle Aged , Signal Transduction , Aged
16.
Clin Oncol (R Coll Radiol) ; 36(7): 409-419, 2024 Jul.
Article En | MEDLINE | ID: mdl-38744596

AIMS: Sarcomas constitute a group of rare malignant neoplasms, commonly subcategorized into soft tissue sarcomas (STS) and bone sarcomas. This study aims to describe the treatment modalities and outcome of head and neck sarcoma (HNS) patients in western Denmark and to identify prognostic factors for overall survival and recurrence in HNS patients. MATERIALS AND METHODS: The Aarhus sarcoma registry, The National Danish Sarcoma Database, and the Danish National Pathology Registry were used to identify HNS adult patients diagnosed between 1979 and 2022. RESULTS: Altogether, 291 patients were included in this study. The prevalent histological subtypes were undifferentiated pleomorphic sarcoma (16%; 48/291) and leiomyosarcoma (15%; 44/291) for STS patients (n = 230) and chondrosarcoma (10%; 28/291) and osteosarcoma (7%; 19/291) for bone sarcoma patients (n = 61). Surgery with curative intent was performed in 71% (164/230) and 70% (43/61) of STS and bone sarcoma patients, respectively. Clear resection was achieved in 59% (97/164) of STS patients and 44% (19/43) of bone sarcoma patients. Eighty-nine patients relapsed (STS n = 66, bone sarcoma n = 23) after a median time of 2.7/5.5 years for STS/bone sarcoma patients. The five-year overall survival rates were 45% for STS patients and 66% for bone sarcoma patients. The following factors were significantly, negatively associated with overall survival in STS patients: Age (hazard ratio (HR)) = 1.02, p < 0.001), tumour size ≥5 cm (HR = 1.75, p = 0.003), metastatic disease (HR = 3.17, p < 0.001), high grade tumour (HR = 2.24, p = 0.004), previous cancer (HR = 2.84, p < 0.001), and high Aarhus composite biomarker score (ACBS) (HR = 4.56, p = 0.001). For relapse in STS patients, higher tumour grade (HR = 3.19, p = 0.014), intralesional margins (HR = 2.84, p < 0.001), ≥2 previous cancers (HR = 3.00, p = 0.004), and high ACBS (HR = 3.29, p = 0.047), were negatively associated. For bone sarcomas only higher age (HR = 1.02, p = 0.049) and intralesional margins (HR = 2.91, p = 0.042) were significant negative factors for overall survival. CONCLUSION: Multiple prognostic factors for overall survival and relapse were identified, especially for STS patients.


Head and Neck Neoplasms , Sarcoma , Humans , Male , Female , Middle Aged , Retrospective Studies , Sarcoma/therapy , Sarcoma/pathology , Sarcoma/mortality , Prognosis , Adult , Head and Neck Neoplasms/therapy , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/mortality , Aged , Young Adult , Adolescent , Aged, 80 and over , Denmark/epidemiology , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/pathology , Treatment Outcome , Survival Rate
17.
J Craniofac Surg ; 35(4): 1272-1275, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38710071

The BiZact device, a bipolar electrosurgical scissor designed for tonsillectomy, minimizes thermal tissue damage and seals blood vessels <3 mm in diameter while dividing the soft tissue. This study describes the authors' experience with sinonasal tumor surgery using a BiZact and discusses its clinical utility and advantages. The authors analyzed BiZact-assisted endoscopic sinonasal tumor surgery cases between January 2021 and May 2023. Data were collected on patients' demographics, histopathology, extent of tumor involvement, surgical records, and postoperative medical records. Clinical utility was assessed using the success rate of complete tumor excision, estimated blood loss during surgery, device-related complications, and operation time. A survey of the surgeons' BiZact experience was also conducted. The diagnoses of the 20 patients in this study included squamous cell carcinoma (n = 2), malignant melanoma (n = 1), sarcoma (n = 1), natural killer cell lymphoma (n = 1), inverted papilloma (n = 12), angiofibroma (n = 2), and schwannoma (n = 1). This pilot study demonstrated a shortened operative time, with a median of 0.8 hours and <100 mL of intraoperative blood loss. In addition, no BiZact-related complications were observed. The BiZact device allows efficient sinonasal surgery because it has the unique advantage of one-step sealing and cutting. BiZact-assisted endoscopic sinonasal tumor surgery is a beneficial and safe procedure that reduces blood loss during surgery, shortens the operative time, and minimizes postoperative complications.


Endoscopy , Operative Time , Paranasal Sinus Neoplasms , Humans , Male , Female , Middle Aged , Adult , Aged , Paranasal Sinus Neoplasms/surgery , Paranasal Sinus Neoplasms/pathology , Endoscopy/methods , Pilot Projects , Electrosurgery/instrumentation , Electrosurgery/methods , Blood Loss, Surgical , Carcinoma, Squamous Cell/surgery , Carcinoma, Squamous Cell/pathology , Melanoma/surgery , Melanoma/pathology , Angiofibroma/surgery , Angiofibroma/pathology , Sarcoma/surgery , Sarcoma/pathology , Treatment Outcome , Papilloma, Inverted/surgery , Papilloma, Inverted/pathology , Aged, 80 and over
18.
Cancer Med ; 13(10): e7252, 2024 May.
Article En | MEDLINE | ID: mdl-38800990

BACKGROUND: Prompt histopathological diagnosis with accuracy is required for soft tissue sarcomas (STSs) which are still challenging. In addition, the advances in artificial intelligence (AI) along with the development of pathology slides digitization may empower the demand for the prediction of behavior of STSs. In this article, we explored the application of deep learning for prediction of prognosis from histopathological images in patients with STS. METHODS: Our retrospective study included a total of 35 histopathological slides from patients with STS. We trained Inception v3 which is proposed method of convolutional neural network based survivability estimation. F1 score which identify the accuracy and area under the receiver operating characteristic curve (AUC) served as main outcome measures from a 4-fold validation. RESULTS: The cohort included 35 patients with a mean age of 64 years, and the mean follow-up period was 34 months (2-66 months). Our deep learning method achieved AUC of 0.974 and an accuracy of 91.9% in predicting overall survival. Concerning with the prediction of metastasis-free survival, the accuracy was 84.2% with the AUC of 0.852. CONCLUSION: AI might be used to help pathologists with accurate prognosis prediction. This study could substantially improve the clinical management of patients with STS.


Artificial Intelligence , Deep Learning , Sarcoma , Humans , Middle Aged , Male , Female , Sarcoma/pathology , Sarcoma/mortality , Retrospective Studies , Prognosis , Aged , Adult , ROC Curve , Neural Networks, Computer , Image Processing, Computer-Assisted/methods , Aged, 80 and over
19.
J Int Med Res ; 52(5): 3000605241253756, 2024 May.
Article En | MEDLINE | ID: mdl-38796313

Prostatic stromal tumors, encompassing prostatic sarcoma and stromal tumors of uncertain malignant potential (STUMP), represent an exceedingly rare category of prostatic diseases, with a prevalence of less than 1%. We present a rare case involving a man in his early 40s diagnosed with STUMP. Despite presenting with normal prostate-specific antigen (PSA) concentrations, the patient experienced persistent dysuria and gross hematuria for >7 months, leading to an initial misdiagnosis of benign prostatic hyperplasia. Persistent symptoms prompted further investigation, with magnetic resonance imaging (MRI) revealing a suspicious lesion on the left side of the prostate, initially thought to be malignant. Transrectal prostatic biopsy subsequently confirmed the presence of mucinous liposarcoma, with no medical history of diabetes, coronary heart disease, or hypertension. The treatment approach comprised robot-assisted laparoscopic radical prostatectomy, culminating in a postoperative pathological definitive diagnosis of STUMP. This case underscores the indispensable role of early MRI in the diagnostic process, highlighting the necessity of detailed pathological examination for a conclusive diagnosis. Our report aims to illuminate the diagnostic challenges and potential treatment pathways for STUMP, emphasizing its consideration in the differential diagnosis of prostatic tumors to advance clinical outcomes in this rare but important condition.


Magnetic Resonance Imaging , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/diagnostic imaging , Adult , Diagnosis, Differential , Prostatectomy , Prostate/pathology , Prostate/surgery , Prostate/diagnostic imaging , Prostate-Specific Antigen/blood , Prostatic Hyperplasia/surgery , Prostatic Hyperplasia/pathology , Prostatic Hyperplasia/diagnostic imaging , Prostatic Hyperplasia/diagnosis , Sarcoma/pathology , Sarcoma/surgery , Sarcoma/diagnosis , Sarcoma/diagnostic imaging
20.
Curr Opin Oncol ; 36(4): 253-262, 2024 Jul 01.
Article En | MEDLINE | ID: mdl-38726834

PURPOSE OF REVIEW: Prognostication of soft tissue sarcomas is challenging due to the diversity of prognostic factors, compounded by the rarity of these tumors. Nomograms are useful predictive tools that assess multiple variables simultaneously, providing estimates of individual likelihoods of specific outcomes at defined time points. Although these models show promising predictive ability, their use underscores the need for further methodological refinement to address gaps in prognosis accuracy. RECENT FINDINGS: Ongoing efforts focus on improving prognostic tools by either enhancing existing models based on established parameters or integrating novel prognostic markers, such as radiomics, genomic, proteomic, and immunologic factors. Artificial intelligence is a new field that is starting to be explored, as it has the capacity to combine and analyze vast and intricate amounts of relevant data, ranging from multiomics information to real-time patient outcomes. SUMMARY: The integration of these innovative markers and methods could enhance the prognostic ability of nomograms such as Sarculator and ultimately enable more accurate and individualized healthcare. Currently, clinical variables continue to be the most significant and effective factors in terms of predicting outcomes in patients with STS. This review firstly introduces the rationale for developing and employing nomograms such as Sarculator, secondly, reflects on some of the latest and ongoing methodological refinements, and provides future perspectives in the field of prognostication of sarcomas.


Nomograms , Sarcoma , Humans , Sarcoma/diagnosis , Sarcoma/pathology , Prognosis , Biomarkers, Tumor/analysis , Artificial Intelligence
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