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Central nervous system tumor with BCOR internal tandem duplication (CNS tumor with BCOR-ITD) constitutes a molecularly distinct entity, characterized by internal tandem duplication within exon 15 of the BCOR transcriptional co-repressor gene (BCOR-ITD). The current study aimed to elucidate the clinical, pathological, and molecular attributes of CNS tumors with BCOR-ITD and explore their putative cellular origin. This study cohort comprised four pediatric cases, aged 23 months to 13 years at initial presentation. Magnetic resonance imaging revealed large, well-circumscribed intra-CNS masses localized heterogeneously throughout the CNS. Microscopically, tumors were composed of spindle to ovoid cells, exhibiting perivascular pseudorosettes and palisading necrosis, but lacking microvascular proliferation. Immunohistochemical staining showed diffuse tumor cell expression of BCOR, CD56, CD99, vimentin, and the stem cell markers PAX6, SOX2, CD133 and Nestin, alongside focal positivity for Olig-2, S100, SOX10, Syn and NeuN. Molecularly, all cases harbored BCOR-ITDs ranging from 87 to 119 base pairs in length, including one case with two distinct ITDs. Notably, the ITDs were interrupted by unique 1-3â¯bp insertions in all cases. In summary, CNS tumors with BCOR-ITD exhibit characteristic clinical, pathological, and molecular features detectable through BCOR immunohistochemistry and confirmatory molecular analyses. Their expression of stem cell markers raises the possibility of an origin from neuroepithelial stem cells rather than representing true embryonal neoplasms.
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Neoplasias del Sistema Nervioso Central , Proteínas Proto-Oncogénicas , Proteínas Represoras , Humanos , Proteínas Represoras/genética , Proteínas Proto-Oncogénicas/genética , Neoplasias del Sistema Nervioso Central/patología , Neoplasias del Sistema Nervioso Central/genética , Neoplasias del Sistema Nervioso Central/metabolismo , Niño , Adolescente , Masculino , Femenino , Lactante , Preescolar , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Secuencias Repetidas en Tándem , Duplicación de GenRESUMEN
OBJECTIVES: Both contrast-enhanced ultrasound (CEUS) and contrast-enhanced magnetic resonance (CEMR) are important imaging methods for hepatocellular carcinoma (HCC). This study aimed to establish a model using preoperative CEUS parameters to predict microvascular invasion (MVI) in HCC, and compare its predictive efficiency with that of CEMR model. METHODS: A total of 93 patients with HCC (39 cases in MVI positive group and 54 cases in MVI negative group) who underwent surgery in our hospital from January 2020 to June 2021 were retrospectively analyzed. Their clinical and imaging data were collected to establish CEUS and CEMR models for predicting MVI. The predictive efficiencies of both models were compared. RESULTS: By the univariate and multivariate regression analyses of patients' clinical information, preoperative CEUS static and dynamic images, we found that serrated edge and time to peak were independent predictors of MVI. The CEUS prediction model achieved a sensitivity of 92.3%, a specificity of 83.3%, and an accuracy of 84.6% (Az: 0.934). By analyzing the clinical and CEMR information, we found that tumor morphology, fast-in and fast-out, peritumoral enhancement, and capsule were independent predictors of MVI. The CEMR prediction model achieved a sensitivity of 97.4%, a specificity of 77.8%, and an accuracy of 83.2% (Az: 0.900). The combination of the two models achieved a sensitivity of 84.6%, a specificity of 87.0%, and an accuracy of 86.2% (Az: 0.884). There was no significant statistical difference in the areas under the ROC curve of the three models. CONCLUSION: The CEUS model and the CEMR model have similar predictive efficiencies for MVI of HCC. CEUS is also an effective method to predict MVI before operation.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/irrigación sanguínea , Neoplasias Hepáticas/irrigación sanguínea , Estudios Retrospectivos , Invasividad Neoplásica , Imagen por Resonancia Magnética/métodosRESUMEN
Preoperative MRI is an essential diagnostic and therapeutic reference for gliomas. This study aims to evaluate the prognostic aspect of a radiomics biomarker for glioma and further investigate its relationship with tumor microenvironment and macrophage infiltration. We covered preoperative MRI of 664 glioma patients from three independent datasets: Jiangsu Province Hospital (JSPH, n = 338), The Cancer Genome Atlas dataset (TCGA, n = 252), and Repository of Molecular Brain Neoplasia Data (REMBRANDT, n = 74). Incorporating a multistep post-processing workflow, 20 radiomics features (Rads) were selected and a radiomics survival biomarker (RadSurv) was developed, proving highly efficient in risk stratification of gliomas (cut-off = 1.06), as well as lower-grade gliomas (cut-off = 0.64) and glioblastomas (cut-off = 1.80) through three fixed cut-off values. Through immune infiltration analysis, we found a positive correlation between RadSurv and macrophage infiltration (RMΦ = 0.297, p < 0.001; RM2Φ = 0.241, p < 0.001), further confirmed by immunohistochemical-staining (glioblastomas, n = 32) and single-cell sequencing (multifocal glioblastomas, n = 2). In conclusion, RadSurv acts as a strong prognostic biomarker for gliomas, exhibiting a non-negligible positive correlation with macrophage infiltration, especially with M2 macrophage, which strongly suggests the promise of radiomics-based models as a preoperative alternative to conventional genomics for predicting tumor macrophage infiltration and provides clinical guidance for immunotherapy.
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Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Glioblastoma/diagnóstico por imagen , Glioblastoma/genética , Glioma/diagnóstico por imagen , Glioma/genética , Glioma/terapia , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , Genómica , Macrófagos , Microambiente TumoralRESUMEN
OBJECTIVE: To evaluate the ability of diffusion-relaxation correlation spectrum imaging (DR-CSI) to predict the consistency and extent of resection (EOR) of pituitary adenomas (PAs). METHODS: Forty-four patients with PAs were prospectively enrolled. Tumor consistency was evaluated at surgery as either soft or hard, followed by histological assessment. In vivo DR-CSI was performed and spectra were segmented following to a peak-based strategy into four compartments, designated A (low ADC), B (mediate ADC, short T2), C (mediate ADC, long T2), and D (high ADC). The corresponding volume fractions ([Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text]) along with the ADC and T2 values were calculated and assessed using univariable analysis for discrimination between hard and soft PAs. Predictors of EOR > 95% were analyzed using logistic regression model and receiver-operating-characteristic analysis. RESULTS: Tumor consistency was classified as soft (n = 28) or hard (n = 16). Hard PAs presented higher [Formula: see text] (p = 0.001) and lower [Formula: see text] (p = 0.013) than soft PAs, while no significant difference was found in other parameters. [Formula: see text] significantly correlated with the level of collagen content (r = 0.448, p = 0.002). Knosp grade (odds ratio [OR], 0.299; 95% confidence interval [CI], 0.124-0.716; p = 0.007) and [Formula: see text] (OR, 0.834, per 1% increase; 95% CI, 0.731-0.951; p = 0.007) were independently associated with EOR > 95%. A prediction model based on these variables yielded an AUC of 0.934 (sensitivity, 90.9%; specificity, 90.9%), outperforming the Knosp grade alone (AUC, 0.785; p < 0.05). CONCLUSION: DR-CSI may serve as a promising tool to predict the consistency and EOR of PAs. CLINICAL RELEVANCE STATEMENT: DR-CSI provides an imaging dimension for characterizing tissue microstructure of PAs and may serve as a promising tool to predict the tumor consistency and extent of resection in patients with PAs. KEY POINTS: ⢠DR-CSI provides an imaging dimension for characterizing tissue microstructure of PAs by visualizing the volume fraction and corresponding spatial distribution of four compartments ([Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text]). ⢠[Formula: see text] correlated with the level of collagen content and may be the best DR-CSI parameter for discrimination between hard and soft PAs. ⢠The combination of Knosp grade and [Formula: see text] achieved an AUC of 0.934 for predicting the total or near-total resection, outperforming the Knosp grade alone (AUC, 0.785).
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Adenoma , Neoplasias Hipofisarias , Humanos , Neoplasias Hipofisarias/diagnóstico por imagen , Neoplasias Hipofisarias/cirugía , Neoplasias Hipofisarias/patología , Imagen de Difusión por Resonancia Magnética/métodos , Curva ROC , Adenoma/diagnóstico por imagen , Adenoma/cirugía , Adenoma/patologíaRESUMEN
Objective: This study aims to identify the risk factors associated with short stature in children born small for gestational age (SGA) at full-term. Methods: This was a retrospective study. The subjects were full-term SGA infants who were followed up until the age of 2 years. The risk factors for short stature were identified with univariate and multivariate analyses. Results: Of 456 full-term SGA children enrolled in this study, 28 cases had short stature at 2 years of age. A significant decrease in placental perfusion was found in the short children group with intravoxel incoherent motion (IVIM) technology, which was an advanced bi-exponential diffusion-weighted imaging (DWI) model of magnetic resonance imaging (MRI) (p = 0.012). Compared to non-short children born SGA at full-term, the short children group underwent an incomplete catch-up growth. Mothers who suffered from systemic lupus erythematosus were more likely to have a short child born SGA (p = 0.023). The morbidity of giant placental chorioangioma was higher in the short children group. The pulsatility index (PI), resistivity index (RI), and systolic-diastolic (S/D) ratio of umbilical artery were higher in the short children group than in the non-short control group (p = 0.042, 0.041, and 0.043). Multivariate analysis demonstrated that decrease of perfusion fraction (f p) in IVIM of placental MRI, chromosomal abnormalities, short parental height, and absence of catch-up growth were associated with a higher risk of short stature in children born SGA at full-term. Conclusion: Risk factors for short stature in full-term SGA children at 2 years of age included a decrease of perfusion fraction f p in IVIM of placental MRI, chromosomal abnormalities, and short parental height.
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Polygoni Multiflori Radix (PMR), the dried root of Polygonum Multiflorum Thunb., has been widely used as traditional Chinese medicines in clinical practice for centuries. However, the frequently reported hepatotoxic adverse effects hindered its safe use in clinical practice. This study aims to explore the hepatotoxic effect of PMR extract and the major PMR derived anthraquinones including emodin, chrysophanol, and physcion in mice and the underlying mechanisms based on bile acid homeostasis. After consecutively treating the ICR mice with PMR extract or individual anthraquinones for 14 or 28 days, the liver function was evaluated by measuring serum enzymes levels and liver histological examination. The compositions of bile acids (BAs) in the bile, liver, and plasma were measured by LC-MS/MS, followed by Principal Component Analysis (PCA) and Partial Least Squares Discriminate Analysis (PLS-DA). Additionally, gene and protein expressions of BA efflux transporters, bile salt export pump (Bsep) and multidrug resistance-associated protein 2 (Mrp2), were examined to investigate the underlying mechanisms. After 14-day administration, mild inflammatory cell infiltration in the liver was observed in the physcion- and PMR-treated groups, while it was found in all the treated groups after 28-day treatment. Physcion and PMR extract induced hepatic BA accumulation after 14-day treatment, but such accumulation was attenuated after 28-day treatment. Based on the PLS-DA results, physcion- and PMR-treated groups were partially overlapping and both groups showed a clear separation with the control group in the mouse liver. The expression of Bsep and Mrp2 in the physcion- and PMR-treated mouse liver was decreased after 14-day treatment, while the downregulation was abrogated after 28-day treatment. Our study, for the first time, demonstrated that both PMR extract and tested anthraquinones could alter the disposition of either the total or individual BAs in the mouse bile, liver, and plasma via regulating the BA efflux transporters and induce liver injury, which provide a theoretical basis for the quality control and safe use of PMR in practice.
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The glioma immune microenvironment (GIM), consisting of glioma cells, stromal cells, and immune cells, accelerates the initiation, development, immune evasion, chemoresistance, and radioresistance of glioblastoma (GBM), whereas the immunosuppressive mechanisms of GBM have not been thoroughly elucidated to date. The glioma data downloaded from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases were used to evaluate the composition of tumor-infiltrating immune cells (TICs) by the CIBERSORT algorithm. RNA-seq datasets from the TCGA and CGGA were used to analyze the relationship between immune scores with patients' characteristics and TICs, which showed higher ratios of tumor-inhibiting/tumor-promoting signatures (M2/M1 macrophages) along with higher immune scores. The distribution of TICs among different glioma patients and the correlation with hazard ratio (HR) analysis suggested that M2 macrophages were abundant in malignant gliomas and indicated an unfavorable prognosis. We further analyzed TCGA cases with available mutation and copy-number alteration information, which showed that the status of PTEN could influence the immune microenvironment of glioma patients. Tissue microarrays of 39 GBM patients were carried out to confirm the clinical significance of PTEN and macrophage markers. We found that the high expression of PTEN was associated with a more extended survival period of glioma patients, positively correlated with M2 macrophages and negatively with M1 macrophages. Transwell and flow cytometry analyses demonstrated that PTEN status could prevent M1 to M2 polarization and M2 macrophage recruitment of gliomas in vitro. The newly discovered immunoregulatory activity of PTEN opens innovative avenues for investigations relevant to counteracting cancer development and progression.
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Glioblastoma , Glioma , Macrófagos , Fosfohidrolasa PTEN , Microambiente Tumoral , Regulación Neoplásica de la Expresión Génica , Glioblastoma/genética , Glioblastoma/patología , Glioma/genética , Glioma/patología , Humanos , Macrófagos/metabolismo , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Pronóstico , Microambiente Tumoral/genéticaRESUMEN
Tumour invasion is closely related to the prognosis and recurrence of glioblastoma multiforme and partially attributes to epithelial-mesenchymal transition. Long intergenic non-coding RNA 00511 (LINC00511) plays a pivotal role in tumour; however, the role of LINC00511 in GBM, especially in the epigenetic molecular regulation mechanism of EMT, is still unclear. Here, we found that LINC00511 was up-regulated in GBM tissues and relatively high LINC00511 expression predicted poorer prognosis. Moreover, ectopic LINC00511 enhanced GBM cells proliferation, EMT, migration and invasion, whereas LINC00511 knockdown had the opposite effects. Mechanistically, we confirmed that ZEB1 acted as a transcription factor for LINC00511 in GBM cells. Subsequently, we found that LINC00511 served as a competing endogenous RNA that sponged miR-524-5p to indirectly regulate YB1, whereas, up-regulated YB1 promoted ZEB1 expression, which inversely facilitated LINC00511 expression. Finally, orthotopic xenograft models were performed to further demonstrate the LINC00511 on GBM tumorigenesis. This study demonstrates that a LINC00511/miR-524-5p/YB1/ZEB1 positive feedback loop provides potential therapeutic targets for GBM progression.
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Carcinogénesis/genética , Transición Epitelial-Mesenquimal/genética , Retroalimentación Fisiológica , Glioblastoma/genética , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , Proteína 1 de Unión a la Caja Y/metabolismo , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismo , Animales , Secuencia de Bases , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Carcinogénesis/patología , Ciclo Celular/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Glioblastoma/patología , Células HEK293 , Humanos , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/genética , Invasividad Neoplásica , Pronóstico , ARN Largo no Codificante/genética , Transcripción Genética , Regulación hacia Arriba/genéticaRESUMEN
Glioblastoma (GBM) is the most universal type of primary brain malignant tumour, and the prognosis of patients with GBM is poor. S100A11 plays an essential role in tumour. However, the role and molecular mechanism of S100A11 in GBM are not clear. Here, we found that S100A11 was up-regulated in GBM tissues and higher S100A11 expression indicated poor prognosis of GBM patients. Overexpression of S100A11 promoted GBM cell growth, epithelial-mesenchymal transition (EMT), migration, invasion and generation of glioma stem cells (GSCs), whereas its knockdown inhibited these activities. More importantly, S100A11 interacted with ANXA2 and regulated NF-κB signalling pathway through decreasing ubiquitination and degradation of ANXA2. Additionally, NF-κB regulated S100A11 at transcriptional level as a positive feedback. We also demonstrated the S100A11 on tumour growth in GBM using an orthotopic tumour xenografting. These data demonstrate that S100A11/ANXA2/NF-κB positive feedback loop in GBM cells that promote the progression of GBM.
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Anexina A2/metabolismo , Neoplasias Encefálicas/genética , Retroalimentación Fisiológica , Glioblastoma/genética , FN-kappa B/metabolismo , Oncogenes , Proteínas S100/metabolismo , Animales , Neoplasias Encefálicas/patología , Carcinogénesis/genética , Carcinogénesis/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Glioblastoma/patología , Humanos , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Invasividad Neoplásica , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Pronóstico , Complejo de la Endopetidasa Proteasomal/metabolismo , Estabilidad Proteica , Proteolisis , Transducción de Señal , Esferoides Celulares/patología , Transcripción Genética , Ubiquitinación , Regulación hacia Arriba/genéticaRESUMEN
Glioblastoma multiforme (GBM) is one of the most hypoxic tumors of the central nervous system. Although temozolomide (TMZ) is an effective clinical agent in the GBM therapy, the hypoxic microenvironment remains a major barrier in glioma chemotherapy resistance, and the underlying mechanisms are poorly understood. Here, we find hypoxia can induce the protective response to mitochondrion via HIF-1α-mediated miR-26a upregulation which is associated with TMZ resistance in vitro and in vivo. Further, we demonstrated that HIF-1α/miR-26a axis strengthened the acquisition of TMZ resistance through prevention of Bax and Bad in mitochondria dysfunction in GBM. In addition, miR-26a expression levels negatively correlate with Bax, Bad levels, and GBM progression; but highly correlate with HIF-1α levels in clinical cancer tissues. These findings provide a new link in the mechanistic understanding of TMZ resistance under glioma hypoxia microenvironment, and consequently HIF-1α/miR-26a/Bax/Bad signaling pathway as a promising adjuvant therapy for GBM with TMZ.
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Neoplasias Encefálicas/genética , Resistencia a Antineoplásicos/genética , Regulación Neoplásica de la Expresión Génica , Glioblastoma/genética , MicroARNs/genética , Proteína X Asociada a bcl-2/genética , Proteína Letal Asociada a bcl/genética , Animales , Antagomirs/genética , Antagomirs/metabolismo , Antineoplásicos Alquilantes/farmacología , Apoptosis/efectos de los fármacos , Apoptosis/genética , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Femenino , Glioblastoma/tratamiento farmacológico , Glioblastoma/metabolismo , Glioblastoma/patología , Humanos , Hipoxia/genética , Hipoxia/metabolismo , Hipoxia/patología , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Ratones , Ratones Desnudos , MicroARNs/antagonistas & inhibidores , MicroARNs/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/patología , Transducción de Señal , Análisis de Supervivencia , Temozolomida/farmacología , Carga Tumoral/efectos de los fármacos , Microambiente Tumoral/genética , Ensayos Antitumor por Modelo de Xenoinjerto , Proteína X Asociada a bcl-2/metabolismo , Proteína Letal Asociada a bcl/metabolismoRESUMEN
Recent data have been shown that EZH2 is a critical oncogene via the repression of tumor suppressor genes in human cancers. In our study, we performed a genome-wide miRNA screen with a bioinformatics analysis to identify EZH2 specific miRNAs. Of these miRNAs, miR-524-5p and miR-324-5p were decreased in glioma tissues, and confered poor prognosis for glioma patients. Upregulation of miR-524-5p and miR-324-5p reduced glioma cell proliferation and increased temozolomide (TMZ) chemosensitivity by targeting EZH2. Importantly, the effection of miR-524-5p and miR-324-5p on cell proliferation and TMZ chemosensitivity in glioma were reversed by expression of EZH2 cDNA. Further, miR-524-5p and miR-324-5p overexpression suppressed glioma growth and prolonged survival in an intracranial xenograft model. Multivariate Cox regression analysis revealed that miR-524-5p was an independent prognostic factor in gliobalstoma patients. Taken together, these data indicate that miRNA-driven EZH2 repression may provide evidence of the molecular mechanism for gliomagenesis and the novel therapeutic targets for glioma.
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Temozolomide (TMZ) is a promising chemotherapeutic agent to treat Glioblastoma multiforme (GBM). However, resistance to TMZ develops quickly with a high frequency. The mechanisms underlying GBM cells' resistance to TMZ are not fully understood. MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate protein expression by cleaving or repressing the translation of target mRNAs. Recently, miRNAs have been discovered to play important roles in drug resistance. A previous study showed that miR-181b in involved in glioma tumorigenesis. Thus, it would be valuable to explore the functions and mechanisms of miR-181b in regulating GMB cells' sensitivity to TMZ. In this study, quantitative real-time reverse transcription PCR (qRT-PCR) data indicated that miR-181b was significantly downregulated in recurrent GBM tissues compared with initial GBM tissues. We also found that miR-181b overexpression increased the chemo-sensitivity of GBM cells to TMZ and potentiated TMZ-induced apoptosis in vitro and in vivo. Moreover, we demonstrated that the epidermal growth factor receptor (EGFR) was a direct target of miR-181b: restoration of EGFR rescued the inhibitory effects of miR-181b and TMZ treatment. Taken together, our data support strongly an important role for miR-181b in conferring TMZ resistance by targeting EGFR expression.
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Antineoplásicos Alquilantes/farmacología , Neoplasias Encefálicas/tratamiento farmacológico , Dacarbazina/análogos & derivados , Receptores ErbB/metabolismo , Glioblastoma/tratamiento farmacológico , MicroARNs/metabolismo , Animales , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Neoplasias Encefálicas/metabolismo , Línea Celular Tumoral , Dacarbazina/farmacología , Resistencia a Antineoplásicos/fisiología , Receptores ErbB/antagonistas & inhibidores , Glioblastoma/metabolismo , Humanos , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Recurrencia Local de Neoplasia , Trasplante de Neoplasias , Distribución Aleatoria , TemozolomidaRESUMEN
An increasing number of TFE3 rearrangement-associated tumors, such as TFE3 rearrangement-associated perivascular epithelioid cell tumors (PEComas), melanotic Xp11 translocation renal cancers, and melanotic Xp11 neoplasms, have recently been reported. We examined 12 such cases, including 5 TFE3 rearrangement-associated PEComas located in the pancreas, cervix, or pelvis and 7 melanotic Xp11 translocation renal cancers, using clinicopathologic, immunohistochemical, and molecular analyses. All the tumors shared a similar morphology, including a purely nested or sheet-like architecture separated by a delicate vascular network, purely epithelioid cells displaying a clear or granular eosinophilic cytoplasm, a lack of papillary structures and spindle cell or fat components, uniform round or oval nuclei containing small visible nucleoli, and, in most cases (11/12), melanin pigmentation. The levels of mitotic activity and necrosis varied. All 12 cases displayed moderately (2+) or strongly (3+) positive immunoreactivity for TFE3 and cathepsin K. One case labeled focally for HMB45 and Melan-A, whereas the others typically labeled moderately (2+) or strongly (3+) for 1 of these markers. None of the cases were immunoreactive for smooth muscle actin, desmin, CKpan, S100, or PAX8. PSF-TFE3 fusion genes were confirmed by reverse transcription polymerase chain reaction in cases (7/7) in which a novel PSF-TFE3 fusion point was identified. All of the cases displayed TFE3 rearrangement associated with Xp11 translocation. Furthermore, we developed a PSF-TFE3 fusion fluorescence in situ hybridization assay for the detection of the PSF-TFE3 fusion gene and detected it in all 12 cases. Clinical follow-up data were available for 7 patients. Three patients died, and 2 patients (cases 1 and 3) remained alive with no evidence of disease after initial resection. Case 2 experienced recurrence and remained alive with disease. Case 5, a recent case, remained alive with extensive abdominal cavity metastases. Our data suggest that these tumors belong to a single clinicopathologic spectrum and expand the known characteristics of TFE3 rearrangement-associated tumors.
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Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Biomarcadores de Tumor/genética , Cromosomas Humanos X , Fusión Génica , Reordenamiento Génico , Inmunohistoquímica , Neoplasias Renales/genética , Melanoma/genética , Técnicas de Diagnóstico Molecular , Neoplasias de Células Epitelioides Perivasculares/genética , Proteínas de Unión al ARN/genética , Translocación Genética , Adolescente , Adulto , Anciano , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/análisis , Biomarcadores de Tumor/análisis , Niño , Femenino , Predisposición Genética a la Enfermedad , Humanos , Hibridación Fluorescente in Situ , Neoplasias Renales/química , Neoplasias Renales/clasificación , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Masculino , Melanoma/química , Melanoma/clasificación , Melanoma/mortalidad , Melanoma/patología , Persona de Mediana Edad , Mitosis , Factor de Empalme Asociado a PTB , Neoplasias de Células Epitelioides Perivasculares/química , Neoplasias de Células Epitelioides Perivasculares/clasificación , Neoplasias de Células Epitelioides Perivasculares/mortalidad , Neoplasias de Células Epitelioides Perivasculares/patología , Fenotipo , Valor Predictivo de las Pruebas , Pronóstico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de TiempoRESUMEN
OBJECTIVE: To study the clinicopathologic characteristics and diagnostic criteria of interdigitating dendritic cell sarcoma/tumor (IDCS/T). METHODS: The clinical features, histologic findings and results of immunohistochemical study in six cases of IDCS/T were analyzed, with review of literature. RESULTS: The age of patients ranged from 20 to 68 years. The sites of involvement included lymph node, tonsil and soft tissue. Histologically, the tumor cells were arranged in sheets, fascicles or whorls and intimately admixed with abundant lymphocytes and plasma cells. They were oval to spindly in shape and contained pale eosinophilic cytoplasm, oval nuclei and distinct nucleoli.Immunohistochemical study showed that the tumor cells were positive for S-100 protein and CD68. CONCLUSIONS: IDCS/T is a rare malignant tumor with poor prognosis. It carries distinctive histologic pattern and immunophenotype. The entity needs to be distinguished from follicular dendritic cell sarcoma/tumor, anaplastic large cell lymphoma and other spindle cell sarcomas in occurring soft tissue.