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1.
Hum Cell ; 37(3): 704-713, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38411836

RESUMO

MYCN (master regulator of cell cycle entry and proliferative metabolism) gene amplification defines a molecular subgroup of spinal cord ependymomas that show high-grade morphology and aggressive behavior. Demonstration of MYCN amplification by DNA methylation or fluorescence-in situ hybridization (FISH) is required for diagnosis. We aimed to (i) assess prevalence and clinicopathological features of MYCN-amplified spinal ependymomas and (ii) evaluate utility of immunohistochemistry (IHC) for MYCN protein as a surrogate for molecular testing. A combined retrospective-prospective study spanning 8 years was designed during which all spinal cord ependymomas with adequate tissue were subjected to MYCN FISH and MYCN IHC. Among 77 spinal cord ependymomas included, MYCN amplification was identified in 4 samples from 3 patients (3/74, 4%) including two (1st and 2nd recurrences) from the same patient. All patients were adults (median age at diagnosis of 32 years) including two females and one male. The index tumors were located in thoracic (n = 2) and lumbar (n = 1) spinal cord. One of the female patients had neurofibromatosis type 2 (NF2). All four tumors showed anaplastic histology. Diffuse expression of MYCN protein was seen in all four MYCN-amplified samples but in none of the non-amplified cases, thus showing 100% concordance with FISH results. On follow-up, the NF2 patient developed widespread spinal dissemination while another developed recurrence proximal to the site of previous excision. To conclude, MYCN-amplified spinal ependymomas are rare tumors, accounting for ~ 4% of spinal cord ependymomas. Within the limitation of small sample size, MYCN IHC showed excellent concordance with MYCN gene amplification.


Assuntos
Ependimoma , Neoplasias da Medula Espinal , Adulto , Humanos , Masculino , Feminino , Proteína Proto-Oncogênica N-Myc/genética , Estudos Retrospectivos , Imuno-Histoquímica , Estudos Prospectivos , Ependimoma/diagnóstico , Ependimoma/genética , Ependimoma/patologia , Neoplasias da Medula Espinal/diagnóstico , Neoplasias da Medula Espinal/genética , Neoplasias da Medula Espinal/patologia , Biomarcadores
2.
Indian J Pathol Microbiol ; 65(Supplement): S68-S72, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35562136

RESUMO

Ependymomas can arise along the entire neuraxis; however, they possess site-specific unique molecular alterations and a methylome pattern which is directly related with the prognostic outcomes. Since 2016, when the updated fourth edition of World Health Organization (WHO) classification of tumors of the central nervous system was published, it has been emphasized to classify ependymomas by anatomic site and molecular signatures associated genetic alterations so that classification of the disease reflects its underlying biology. In continuation, the fifth edition of the WHO classification of CNS tumors introduces major changes, including site-specific molecular profiles as the basis of classifying ependymomas. Furthermore, an integrated tier system of reporting is recommended for better clinical correlation and predicting outcomes. WHO grading can still be included in a specific tier, along with molecular markers.


Assuntos
Neoplasias do Sistema Nervoso Central , Ependimoma , Neoplasias Supratentoriais , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/genética , Ependimoma/diagnóstico , Ependimoma/genética , Humanos , Prognóstico , Neoplasias Supratentoriais/genética , Neoplasias Supratentoriais/patologia , Organização Mundial da Saúde
3.
Neuropathology ; 41(5): 412-421, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34558124

RESUMO

Ependymoma is a relatively rare glial tumor of the central nervous system that arise from the cells lining the ventricles and central canal of the spinal cord. Ependymosarcoma (ES) is a newly introduced tumor entity of uncertain prognosis characterized by a rare phenomenon of a malignant mesenchymal transition arising within an ependymoma. ESs are surgically challenging tumors for diagnosis and therapy with a high incidence of morbidity and mortality. Here, we report two diagnostically challenging cases of primary ES in a 25-year-old female and a 17-year-old male. Both the cases presented with progressive and sequential neurological deficits over a period of five to eight months, and histological examination revealed a biphasic gliomesenchymal architecture comprised of anaplastic ependymomatous and sarcomatous components. Molecular genetic analysis revealed the presence of type 1 C11orf95:RELA fusion transcript. To date, 22 cases of ES have been reported in the literature, and only one case harbored type 1 C11orf95:RELA fusion transcript.


Assuntos
Ependimoma , Glioma , Adolescente , Adulto , Feminino , Humanos , Masculino , Prognóstico , Proteínas , Fator de Transcrição RelA
4.
Sci Rep ; 11(1): 3963, 2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-33597669

RESUMO

Studying respiratory illness-specific microbial signatures and their interaction with other micro-residents could provide a better understanding of lung microbial ecology. Each respiratory illness has a specific disease etiology, however, so far no study has revealed disease-specific microbial markers. The present study was designed to determine disease-specific microbial features and their interactions with other residents in chronic obstructive pulmonary diseases (stable and exacerbated), sarcoidosis, and interstitial lung diseases. Broncho-alveolar lavage samples (n = 43) were analyzed by SSU rRNA gene sequencing to study the alveolar microbiome in these diseases. A predominance of Proteobacteria followed by Firmicutes, Bacteroidetes, Actinobacteria, and Fusobacteria was observed in all the disease subsets. Shannon diversity was significantly higher in stable COPD when compared to exacerbated chronic obstructive pulmonary disease (ECOPD) (p = 0.0061), and ILD patient samples (p = 0.037). The lung microbiome of the patients with stable COPD was more diverse in comparison to ECOPD and ILD patients (p < 0.001). Lefse analysis identified 40 disease-differentiating microbial features (LDA score (log10) > 4). Species network analysis indicated a significant correlation (p < 0.05) of diseases specific microbial signature with other lung microbiome members. The current study strengthens the proposed hypothesis that each respiratory illness has unique microbial signatures. These microbial signatures could be used as diagnostic markers to differentiate among various respiratory illnesses.


Assuntos
Doenças Pulmonares Intersticiais/microbiologia , Doença Pulmonar Obstrutiva Crônica/microbiologia , Sarcoidose/microbiologia , Idoso , Bactérias/genética , Lavagem Broncoalveolar , Diagnóstico Diferencial , Feminino , Humanos , Pulmão/microbiologia , Masculino , Microbiota/genética , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética
6.
Brain Tumor Pathol ; 38(1): 30-40, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33130928

RESUMO

The PFA molecular subgroup of posterior fossa ependymomas (PF-EPNs) shows poor outcome. H3K27me3 (me3) loss by immunohistochemistry (IHC) is a surrogate marker for PFA wherein its loss is attributed to overexpression of Cxorf67/EZH2 inhibitory protein (EZHIP), C17orf96, and ATRX loss. We aimed to subgroup PF-EPNs using me3 IHC and study correlations of the molecular subgroups with other histone related proteins, 1q gain, Tenascin C and outcome. IHC for me3, acetyl-H3K27, H3K27M, ATRX, EZH2, EZHIP, C17orf96, Tenascin-C, and fluorescence in-situ hybridisation for chromosome 1q25 locus were performed on an ambispective PF-EPN cohort (2003-2019). H3K27M-mutant gliomas were included for comparison. Among 69 patients, PFA (me3 loss) constituted 64%. EZHIP overexpression and 1q gain were exclusive to PFA seen in 72% and 19%, respectively. Tenascin C was more frequently positive in PFA (p = 0.02). H3K27M expression and ATRX loss were noted in one case of PFA-EPN each. All H3K27M-mutant gliomas (n = 8) and PFA-EPN (n = 1) were EZHIP negative. C17orf96 and acetyl-H3K27 expression did not correlate with me3 loss. H3K27me3 is a robust surrogate for PF-EPN molecular subgrouping. EZHIP overexpression was exclusive to PFA EPNs and was characteristically absent in midline gliomas and the rare PFA harbouring H3K27M mutations representing mutually exclusive pathways leading to me3 loss.


Assuntos
Neoplasias Encefálicas/genética , Dura-Máter , Ependimoma/genética , Expressão Gênica , Histona Desmetilases com o Domínio Jumonji/genética , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Mutação , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/metabolismo , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Adulto Jovem
7.
Brain Tumor Pathol ; 36(4): 152-161, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31388782

RESUMO

Immune check-point blockade (ICB) targeting programmed cell death ligand-1 (PD-L1)/programmed death-1 (PD-1) axis has created paradigm shift in cancer treatment. 'ST-RELA' and 'PF-A' molecular subgroups of ependymomas (EPN) show poor outcomes. We aimed to understand the potential candidature of EPNs for ICB. Supratentorial (ST) Grade II/III EPNs were classified into ST-RELA, ST-YAP, and ST-not otherwise specified (NOS), based on RELA/YAP1 fusion transcripts and/or L1CAM and p65 protein expression. Posterior fossa (PF) EPNs were classified into PF-A and PF-B based on H3K27me3 expression. Immunohistochemistry for PD-L1 and CD8 was performed. RelA protein enrichment at PDL1 promoter site was analysed by chromatin immunoprecipitation-qPCR (ChIP-qPCR). Eighty-three intracranial EPNs were studied. Median tumor infiltrating CD8 + cytotoxic T-lymphocyte (CTL) density was 6/mm2, and was higher in ST-EPNs (median 10/mm2) as compared to PF-EPNs (median 3/mm2). PD-L1 expression was noted in 17/83 (20%) EPNs, including 12/31 ST-RELA and rare ST-NOS (2/12), PF-A (2/25) and PF-B (1/13) EPNs. Twelve EPNs (14%) showed high CTL density and concurrent PD-L1 positivity, of which majority (10/12) were ST-RELA EPNs. Enrichment of RelA protein was seen at PDL1 promoter. Increased CTL densities and upregulation of PD-L1 in ST-RELA ependymomas suggests potential candidature for immunotherapy.


Assuntos
Antígeno B7-H1/genética , Ependimoma/imunologia , Ependimoma/patologia , Linfócitos T Citotóxicos/patologia , Antígeno B7-H1/metabolismo , Ependimoma/genética , Feminino , Humanos , Imuno-Histoquímica , Imunoterapia/métodos , Masculino , Molécula L1 de Adesão de Célula Nervosa/metabolismo , Neoplasias Supratentoriais/patologia , Fator de Transcrição RelA/metabolismo
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