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OBJECTIVE: The current study aimed to investigate the characteristics of tumor-associated macrophages (TAMs) and their association with microvascular density (MVD) in tumor progression in different grades of orofacial squamous cell carcinoma (OSCC) in the Pakistani population. STUDY DESIGN: This prospective study included 234 patients with oral cancer reported at different hospitals in Pakistan diagnosed with OSCC. Tumors were graded on the Anneroth grading system and the association between the frequency of TAMs and MVD was examined in vivo. The macrophages visible through immunohistochemistry for CD68 and the microvessels observed through immunohistochemistry for CD34 were manually counted in 3 high-power fields. RESULTS: The CD68 and CD34 counts were significantly lower in well-differentiated squamous cell carcinoma compared to poorly differentiated squamous cell carcinoma. Linear regression analysis revealed a positive correlation between the area percentage of CD68 immunoreactivity and the grade of the tumor (r = 0.776). Vice versa, a positive correlation also existed between the area percentage of CD34 immunoreactivity and the grade of the tumor (r = 0.690). Pearson correlation revealed a positive association between the TAMs and MVD (r = 0.680; P < .001). CONCLUSIONS: There was an increased population of tumor-associated macrophages and tumor angiogenesis with the increasing grade of orofacial squamous cell carcinoma. (Oral Surg Oral Med Oral Pathol Oral Radiol YEAR;VOL:page range).
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Antígenos de Diferenciación Mielomonocítica , Carcinoma de Células Escamosas , Progresión de la Enfermedad , Inmunohistoquímica , Densidad Microvascular , Neoplasias de la Boca , Clasificación del Tumor , Macrófagos Asociados a Tumores , Humanos , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/irrigación sanguínea , Neoplasias de la Boca/patología , Neoplasias de la Boca/irrigación sanguínea , Macrófagos Asociados a Tumores/patología , Anciano , Adulto , Antígenos CD/análisis , Neovascularización Patológica/patología , Antígenos CD34 , Molécula CD68RESUMEN
Background and Objectives: This study presents a retrospective analysis of 26 autopsy cases from a single centre, primarily focusing on forensic cases, with a majority of male individuals. Materials and Methods: We systematically analysed autopsy reports and cardiac tissue slides using haematoxylin-eosin stain and immunohistochemistry for CD3, CD163, and IL-6. The histological assessment evaluated key variables such as inflammation severity, necrosis, and background changes using a standardised grading system. Quantitative analysis of immunohistochemical markers was performed, calculating the percentage of positively stained cells within the inflammatory infiltrate. Results: The average age was 51.6 years, slightly skewed towards older males. The fatalities varied widely, with sudden death and drug abuse being the most common conditions linked to myocarditis findings on histological examination. A strong correlation was found between the severity of inflammation (measured by size within a myocardium section) and the scoring system based on the number of inflammatory foci per section (p ≤ 0.001). Most cases showed mild to minimal fibrosis, with some exhibiting moderate to severe fibrosis, arteriosclerosis, and myocyte hypertrophy. The presence of protein CD3 in the inflammatory infiltrate revealed a moderate inverse correlation between the CD3 values and the severity of inflammation and necrosis, and a strong inverse correlation with neutrophil levels. CD3 levels were higher in sudden death cases and lower in cases with numerous inflammatory foci, highlighting the discreet nature of lymphocytic myocarditis. Macrophage presence, assessed using CD163, showed a moderate inverse correlation with neutrophil levels and significant differences between sudden death and non-sudden death cases. Macrophage-rich inflammation was observed in cases with pneumonia/bronchopneumonia-associated lesions. IL-6 expression showed a moderate direct correlation with inflammation severity (p = 0.028), severity of necrosis (p = 0.005), and the number of inflammatory foci per section (p = 0.047). A moderate inverse correlation was found between CD3 and IL-6 expression (p = 0.005). Conclusions: These findings highlight the need for a unique immunohistochemical approach in forensic cases of myocarditis, differing from guidelines for endomyocardial biopsies due to diverse inflammatory cells. The study suggests exploring inflammatory chemokines within myocarditis foci for their significance in clinical scenarios. Specifically, IL-6, a crucial pro-inflammatory interleukin, correlated significantly with the severity of inflammation and necrosis (p < 0.05). This study provides novel and valuable insights into the histopathological and immunological markers of myocarditis in autopsy cases.
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Autopsia , Inmunohistoquímica , Miocarditis , Humanos , Miocarditis/patología , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Inmunohistoquímica/métodos , Adulto , Femenino , Anciano , Antígenos CD/análisis , Antígenos de Diferenciación Mielomonocítica/análisis , Complejo CD3/análisis , Interleucina-6/análisis , Miocardio/patología , Receptores de Superficie Celular/análisisRESUMEN
Langerhans cell histiocytosis (LCH) is a myeloid neoplasm characterized by clonal neoplastic proliferation of Langerhans-type dendritic cells associated with an inflammatory infiltrate predominantly composed of lymphocytes and eosinophils. In this article, we present an unusual case of LCH with significant swelling in the left lacrimal sac region in a 3-year-old child, clinically mimicking acute dacryocystitis. Microscopically, it showed intense inflammatory infiltrate and histiocytes with irregular nuclei. The tumor cells were positive for S-100 protein, CD1a, and CD207 (langerin). Molecular study was positive for the V600E/E2/D mutation (EXON 15). This case emphasizes the importance of careful clinical, radiographic, and microscopic evaluation, as some neoplasms may mimic common benign lesions.
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Dacriocistitis , Histiocitosis de Células de Langerhans , Humanos , Histiocitosis de Células de Langerhans/diagnóstico , Histiocitosis de Células de Langerhans/diagnóstico por imagen , Dacriocistitis/diagnóstico , Diagnóstico Diferencial , Preescolar , Enfermedad Aguda , Masculino , Antígenos CD/análisis , Antígenos CD1RESUMEN
BACKGROUND: Contrast enhancement of intracranial aneurysm wall during MRI with targeted visualization of vascular wall correlates with previous aneurysm rupture and, according to some data, may be a predictor of further rupture of unruptured aneurysms. OBJECTIVE: To analyze possible causes of aneurysm contrast enhancement considering morphological data of aneurysm walls. MATERIAL AND METHODS: The study included 44 patients with intracranial aneurysms who underwent preoperative MRI between November 2020 and September 2022. Each aneurysm was assessed regarding contrast enhancement pattern. Microsurgical treatment of aneurysm was accompanied by resection of its wall for subsequent histological and immunohistochemical analysis regarding thrombosis, inflammation and neovascularization. Specimens were subjected to histological and immunochemical analysis. Immunohistochemical analysis was valuable to estimate inflammatory markers CD68 and CD3, as well as neurovascularization marker SD31. RESULTS: Aneurysms with contrast-enhanced walls were characterized by higher number of CD3+, CD68+, CD31+ cells and parietal clots. Intensity of contrast enhancement correlated with aneurysm wall abnormalities. CONCLUSION: Contrast enhancement of aneurysm wall can characterize various morphological abnormalities.
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Aneurisma Intracraneal , Imagen por Resonancia Magnética , Humanos , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/cirugía , Aneurisma Intracraneal/patología , Masculino , Femenino , Persona de Mediana Edad , Imagen por Resonancia Magnética/métodos , Neuroimagen/métodos , Antígenos de Diferenciación Mielomonocítica/análisis , Antígenos de Diferenciación Mielomonocítica/metabolismo , Adulto , Medios de Contraste , Antígenos CD/análisis , Antígenos CD/metabolismo , Anciano , Aneurisma Roto/diagnóstico por imagen , Aneurisma Roto/cirugía , Aneurisma Roto/patología , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/análisis , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Complejo CD3/análisis , Complejo CD3/metabolismo , Molécula CD68RESUMEN
Endometriosis's pathophysiology remains incompletely understood, with evidence pointing towards a dysregulated immune response. Regulatory T (Treg) cells, pivotal in maintaining self-tolerance, may facilitate the survival of ectopic endometrial cells within the abdominal cavity, thereby contributing to endometriosis development. This study aimed to assess the prevalence of CD39+CD73+ suppressor Treg cell subsets in the peripheral blood of endometriosis patients. This research focuses on the pivotal role of regulatory T-cells (Tregs), which are essential for maintaining immune tolerance and preventing autoimmune diseases. A case-control study was conducted, including 32 women diagnosed with endometriosis and 22 control subjects. The frequency of peripheral blood CD39+CD73+ suppressor Treg cells was quantified using flow cytometry. No significant differences were observed in the frequency of CD3+CD4+CD25High cells (Median [M]: 10.1; Interquartile Range [IQR]: 6.32â18.3 vs. M: 9.72; IQR: 6.22-19.8) or CD3+CD4+CD25HighCD39+Foxp3+ cells (M: 31.1; IQR: 19.7-44.0 vs. M: 30.55; IQR: 18.5-45.5) between controls and patients. However, a significantly lower frequency of CD3+CD4+CD25HighCD39+CD73+ cells was observed in the endometriosis group compared to controls (M: 1.98; IQR: 0.0377-3.17 vs. M: 2.25; IQR: 0.50-4.08; p = 0.0483), suggesting a reduction in systemic immune tolerance among these patients. This finding highlights the potential role of CD39 and CD73 expression on Treg cells as biomarkers for assessing disease severity and progression. Furthermore, elucidating the mechanisms driving these alterations may unveil new therapeutic strategies to restore immune equilibrium and mitigate endometriosis symptoms.
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Apirasa , Endometriosis , Citometría de Flujo , Factores de Transcripción Forkhead , Linfocitos T Reguladores , Humanos , Femenino , Endometriosis/inmunología , Endometriosis/sangre , Linfocitos T Reguladores/inmunología , Adulto , Estudios de Casos y Controles , Factores de Transcripción Forkhead/sangre , Factores de Transcripción Forkhead/análisis , Apirasa/análisis , 5'-Nucleotidasa/sangre , Adulto Joven , Antígenos CD/sangre , Antígenos CD/análisis , Estadísticas no Paramétricas , Valores de ReferenciaRESUMEN
Non muscle invasive bladder cancer (NMIBC) has unpredictable outcomes with a variable risk of recurrence and progression. Many clinic-pathological prognostic factors have been identified but remain insufficient, raising the need to investigate new biomarkers. The aim of our study was to assess the prognostic value of the immunohistochemical (IHC) markers E-Cadherin and B-Catenin in NMIBC. All cases of NMIBC were collected between 2008 and 2013. IHC analysis was performed using E-Cadherin and B-Catenin. Reduced or loss of E-Cadherin expression was assessed as abnormal. Only cases with B-Catenin intense membranous staining were considered normal. A correlation was found between abnormal E-Cadherin expression and stage (p = 0.001), grade (p = 0.0000000), recurrence (p = 0.0000000), progression (p = 0.01), recurrence-free survival (p = 0.00000001), and progression-free survival (p = 0.01). A statistically significant association was found between B-Catenin and stage (p = 0. 05), grade (p = 0.02), and recurrence (p = 0.02). The abnormal expression of these markers could help to identify a high-risk subgroup of NMIBC that might benefit from either more accurate follow-up or more aggressive treatment.
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Cadherinas , Neoplasias de la Vejiga Urinaria , beta Catenina , Humanos , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/diagnóstico , Cadherinas/metabolismo , Cadherinas/análisis , Masculino , Femenino , beta Catenina/metabolismo , beta Catenina/análisis , Persona de Mediana Edad , Anciano , Pronóstico , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/análisis , Anciano de 80 o más Años , Invasividad Neoplásica , Adulto , Antígenos CD/metabolismo , Antígenos CD/análisis , Inmunohistoquímica , Neoplasias Vesicales sin Invasión MuscularRESUMEN
Assessing minimal residual disease (MRD) in B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) is essential for adjusting therapeutic strategies and predicting relapse. Quantitative polymerase chain reaction (qPCR) is the gold standard for MRD. Alternatively, flow cytometry is a quicker and cost-effective method that typically uses leukaemia-associated immunophenotype (LAIP) or different-from-normal (DFN) approaches for MRD assessment. This study describes an optimized 12-colour flow cytometry antibody panel designed for BCP-ALL diagnosis and MRD monitoring in a single tube. This method robustly differentiated hematogones and BCP-ALL cells using two specific markers: CD43 and CD81. These and other markers (e.g. CD73, CD66c and CD49f) enhanced the specificity of BCP-ALL cell detection. This innovative approach, based on a dual DFN/LAIP strategy with a principal component analysis method, can be used for all patients and enables MRD analysis even in the absence of a diagnostic sample. The robustness of our method for MRD monitoring was confirmed by the strong correlation (r = 0.87) with the qPCR results. Moreover, it simplifies and accelerates the preanalytical process through the use of a stain/lysis/wash method within a single tube (<2 h). Our flow cytometry-based methodology improves the BCP-ALL diagnosis efficiency and MRD management, offering a complementary method with considerable benefits for clinical laboratories.
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Citometría de Flujo , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Humanos , Neoplasia Residual/diagnóstico , Citometría de Flujo/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Inmunofenotipificación/métodos , Masculino , Estudios de Seguimiento , Femenino , Niño , Toma de Decisiones Clínicas , Antígenos CD/análisis , PreescolarRESUMEN
INTRODUCTION: Despite extensive research, comprehensive characterization of leukaemic stem cells (LSC) and information on their immunophenotypic differences from normal haematopoietic stem cells (HSC) is lacking. Herein, we attempted to unravel the immunophenotypic (IPT) characteristics and heterogeneity of LSC using multiparametric flow cytometry (MFC) and single-cell sequencing. MATERIALS AND METHODS: Bone marrow aspirate samples from patients with acute myeloid leukaemia (AML) were evaluated using MFC at diagnostic and post induction time points using a single tube-10-colour-panel containing LSC-associated antibodies CD123, CD45RA, CD44, CD33 and COMPOSITE (CLL-1, TIM-3, CD25, CD11b, CD22, CD7, CD56) with backbone markers that is, CD45, CD34, CD38, CD117, sCD3. Single-cell sequencing of the whole transcriptome was also done in a bone marrow sample. RESULTS: LSCs and HSCs were identified in 225/255 (88.2%) and 183/255 (71.6%) samples, respectively. Significantly higher expression was noted for COMPOSITE, CD45RA, CD123, CD33, and CD44 in LSCs than HSCs (p < 0.0001). On comparing the LSC specific antigen expressions between CD34+ (n = 184) and CD34- LSCs (n = 41), no difference was observed between the groups. More than one sub-population of LSC was demonstrated in 4.4% of cases, which further revealed high concordance between MFC and single cell transcriptomic analysis in one of the cases displaying three LSC subpopulations by both methods. CONCLUSION: A single tube-10-colour MFC panel is proposed as an easy and reproducible tool to identify and discriminate LSCs from HSCs. LSCs display both inter- and intra-sample heterogeneity in terms of antigen expressions, which opens the facets for single cell molecular analysis to elucidate the role of subpopulations of LSCs in AML progression.
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Citometría de Flujo , Inmunofenotipificación , Leucemia Mieloide Aguda , Células Madre Neoplásicas , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/metabolismo , Citometría de Flujo/métodos , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Análisis de la Célula Individual/métodos , Antígenos CD/metabolismo , Antígenos CD/análisis , AncianoRESUMEN
PURPOSE: Stereotactic body radiation therapy (SBRT) versus surgery for operable early-stage non-small cell lung cancer (ES-NSCLC) remains highly debated. Herein, we used spatial proteomics to identify whether any molecular biomarker(s) associate with the efficacy of either modality, in efforts to optimize treatment selection between surgery and SBRT for this population. METHODS AND MATERIALS: We evaluated biopsy tissue samples from 44 patients with ES-NSCLC treated with first-line SBRT (cohort 1) by GeoMx Digital Spatial Profiling (DSP) with a panel of 70 proteins in 5 spatial molecular compartments: tumor (panCK+), leukocyte (CD45+), lymphocyte (CD3+), macrophage (CD68+), and stroma (α-SMA+). To validate the findings in cohort 1, biopsy samples from 52 patients with ES-NSCLC who received SBRT (cohort 2) and 62 patients with ES-NSCLC who underwent surgery (cohort 3) were collected and analyzed by multiplex immunofluorescence (mIF). RESULTS: In cohort 1, higher CD44 expression in the lymphocyte compartment was associated with poorer recurrence-free survival (RFS) (DSP: P < .001; mIF: P < .001) and higher recurrence rate (DSP: P = .001; mIF: P = .004). mIF data from cohort 2 validated these findings (P < .05 for all). From cohort 3, higher lymphocyte CD44 predicted higher RFS after surgery (P = .003). Intermodality comparisons demonstrated that SBRT was associated with significantly higher RFS over surgery in CD44-low patients (P < .001), but surgery was superior to SBRT in CD44-high cases (P = .016). CONCLUSIONS: Lymphocyte CD44 may not only be a predictor of SBRT efficacy in this population but also an important biomarker (pending validation by large prospective data) that could better sharpen selection for SBRT versus surgery in ES-NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Receptores de Hialuranos , Neoplasias Pulmonares , Linfocitos , Radiocirugia , Humanos , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Receptores de Hialuranos/análisis , Receptores de Hialuranos/metabolismo , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Masculino , Femenino , Anciano , Persona de Mediana Edad , Antígenos de Diferenciación Mielomonocítica/análisis , Antígenos de Diferenciación Mielomonocítica/metabolismo , Antígenos CD/análisis , Antígenos Comunes de Leucocito/análisis , Antígenos Comunes de Leucocito/metabolismo , Anciano de 80 o más Años , Complejo CD3/análisis , Complejo CD3/metabolismo , Estadificación de Neoplasias , Biomarcadores de Tumor/análisis , Selección de Paciente , Molécula CD68RESUMEN
ABSTRACT: Histiocytic disorders mostly occur as de-novo nodal or extranodal benign masses with rare secondary malignant transformation. A 10-year-old female presented with 10-cm cervical swelling since 9 months associated with fever. Computed tomography revealed left cervical lymphadenopathy and bilateral lung nodules. Lymph node excision biopsy showed effacement of architecture by atypical histiocytes with marked nuclear pleomorphism and frequent mitosis. Focal areas showed mature histiocytes with emperipolesis. The cells were immunopositive for CD68, CD163, and S100 (focal), whereas they were negative for Langerin and CD1a. The Ki67 proliferative index was 30%. A diagnosis of histiocytic sarcoma in a background of Rosai-Dorfman disease was made.
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Antígenos CD , Antígenos de Diferenciación Mielomonocítica , Sarcoma Histiocítico , Histiocitosis Sinusal , Inmunohistoquímica , Tomografía Computarizada por Rayos X , Humanos , Femenino , Sarcoma Histiocítico/diagnóstico , Sarcoma Histiocítico/patología , Histiocitosis Sinusal/diagnóstico , Histiocitosis Sinusal/patología , Niño , Antígenos CD/análisis , Proteínas S100/análisis , Histiocitos/patología , Ganglios Linfáticos/patología , Biopsia , Histocitoquímica , Transformación Celular Neoplásica , Microscopía , Receptores de Superficie Celular/genética , Linfadenopatía/patología , Molécula CD68RESUMEN
INTRODUCTION: Lymphocyte subset enumeration by flow cytometry is important for the therapeutic monitoring of a range of conditions. However, current bead-based methodologies do not produce metrologically traceable results. Here we compare an established bead-based methodology with a volumetric-based system traceable to an internationally recognised reference method. METHOD: A total of 118 samples received for lymphocyte subset analysis were tested using an established bead-based technique (BD Multitest™ 6-colour TBNK assay using Trucount™ tubes on a BD FACSLyric flow cytometer), followed by a volumetric method on the Sysmex XF-1600 flow cytometer using Exbio Kombitest 6-colour TBNK reagent. All samples were tested in accordance with the manufacturer's instructions. RESULTS: Absolute count values from both methodologies for CD3+, CD3 + CD4+, CD3 + CD8+, CD19+ and CD3-CD16+/CD56+ lymphocyte populations were compared using linear regression (R2 for all parameters >0.95) and Bland-Altman analysis. There was no significant bias (where p < 0.05) for absolute CD3 + CD4+ lymphocytes in the defined therapeutic range of 0-250 cells/µL (mean bias: 0.27 cells/µL). Although positive biases were seen for CD3 + CD4+ lymphocytes (over the entire range tested: 14-1798 cells/µL) and CD3-CD16+/CD56+ lymphocytes (mean bias: 10.83 cells/µL and 6.79 cells/µL, respectively). Negative biases were seen for CD3 + CD8+ and CD19+ lymphocytes (mean bias: -29.17 cells/µL and - 18.76 cells/µL, respectively). CONCLUSION: A high degree of correlation was found for results from both methodologies and observed bias was within the limits of clinical acceptability for all populations. This shows that the metrologically traceable lymphocyte subset absolute counts produced by the Sysmex XF-1600 are robust within clinically required limits.
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Citometría de Flujo , Subgrupos Linfocitarios , Citometría de Flujo/métodos , Citometría de Flujo/normas , Humanos , Recuento de Linfocitos/normas , Recuento de Linfocitos/métodos , Antígenos CD/análisis , Inmunofenotipificación/normas , Inmunofenotipificación/métodos , FemeninoRESUMEN
OBJECTIVES: Epstein-Barr virus-positive large B-cell lymphoma (EBV+ LBCL) is a heterogeneous group of diseases that may resemble classic Hodgkin lymphoma (CHL) both morphologically and immunophenotypically. However, these diseases are treated with different therapies and carry distinct prognoses. We examined CD200 expression by immunohistochemistry in EBV+ LBCL and evaluated its diagnostic utility in the differential diagnosis with CHL. METHODS: CD200 immunohistochemistry was performed on archival material from 20 cases of CHL (11 EBV+, 9 EBV-), 11 cases of EBV+ LBCL, and 10 cases of diffuse large B-cell lymphoma, not otherwise specified (DLBCL NOS). Staining pattern and intensity (0-3+ scale) were recorded. RESULTS: CD200 positivity was seen in Reed-Sternberg cells in 19 (95%) of 20 cases of CHL, predominantly in a strong (3+, 15/19) and diffuse (>50% of cells, 17/19) pattern. In contrast, CD200 was negative in 8 (73%) of 11 cases of EBV+ LBCL; the 3 positive cases showed 1 to 2+ staining in less than 50% of lesional cells. All cases of DLBCL NOS were negative for CD200. CONCLUSIONS: CD200 may be a useful immunophenotypic marker in differentiating EBV+ LBCL from CHL, with negative to partial/weak staining favoring a diagnosis of EBV+ LBCL and strong diffuse staining favoring a diagnosis of CHL.
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Antígenos CD , Infecciones por Virus de Epstein-Barr , Enfermedad de Hodgkin , Linfoma de Células B Grandes Difuso , Humanos , Infecciones por Virus de Epstein-Barr/diagnóstico , Herpesvirus Humano 4 , Enfermedad de Hodgkin/diagnóstico , Inmunohistoquímica , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/virología , Antígenos CD/análisisRESUMEN
BACKGROUND: Aberrant phenotypes in acute myeloid leukemia have variable frequencies and their prognostic value with adverse hematological and other biological prognostic factors is still controversial, despite several reports of clinical significance. To date, no study has been reported evaluating the incidence of these phenotypic aberrations in the Moroccan population. The aim is to evaluate the incidence of aberrant phenotype expressions in acute myeloid leukemia and correlate their presence with the different AML subtypes, and clinical and biological characteristics in Moroccan patients. METHODS: Fifty-four AML patients were diagnosed according to WHO classification 2016 criteria. Immunopheno-typing by flow cytometric analysis was performed to evaluate aberrant phenotypes on myeloblasts. RESULTS: The occurrence of lymphoid antigens in AML was higher (51.8%), which was closer to that reported in the literature. CD7 has been revealed to be the most commonly expressed lymphoid antigen. Besides, CD19 was expressed in all 3.7% of M2 AML subtype. However, we could find no statistically significant differences between these aberrant phenotypes regarding FAB subtypes or clinical and biological outcomes. The great majority of AML cases showed asynchronous expression (57%) with significant differences regarding FAB subtypes. CONCLUSIONS: Aberrant phenotypes might be associated with different leukemia subtypes that should be studied for a better understanding of their biological significance and adding important information for prognosis and, at the same time, could be of help when looking for minimal residual disease during morphologic remission.
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Hematología , Leucemia Mieloide Aguda , Antígenos CD/análisis , Antígenos CD/genética , Hospitales , Humanos , Inmunofenotipificación , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Marruecos/epidemiología , Fenotipo , PronósticoRESUMEN
Nivolumab, an immune checkpoint blocker, has been approved for advanced gastric cancer (GC), but predictive factors of nivolumab's efficacy in patients with GC, especially immune cells such as tissue-resident memory T cells or those forming tertiary lymphoid structures (TLS), remain unclear. Tissue samples were obtained from surgically resected specimens of patients with GC who were treated with nivolumab as third-line or later treatment. Immunohistochemical staining was performed to detect the presence of TLS and CD103+ T cells and assess the association between TLSs and response to nivolumab treatment. A total of 19 patients were analyzed. In patients with partial response (PR) to nivolumab, numerous TLS were observed, and CD103+ T cells were found in and around TLS. Patients with many TLS experienced immune-related adverse events more often than those with few TLS (p = 0.018). The prognosis of patients with TLS high was better than those with TLS low. Patients with a combination of TLS high and CD103 high tended to have a better prognosis than other groups. Our results suggested that TLS status might be a predictor of nivolumab effectiveness.
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Antineoplásicos Inmunológicos/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Nivolumab/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Estructuras Linfoides Terciarias/tratamiento farmacológico , Anciano , Antígenos CD/análisis , Femenino , Humanos , Cadenas alfa de Integrinas/análisis , Masculino , Células T de Memoria/efectos de los fármacos , Células T de Memoria/patología , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Pronóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Estructuras Linfoides Terciarias/diagnóstico , Estructuras Linfoides Terciarias/patología , Resultado del TratamientoRESUMEN
Invariant NK T (iNKT) cells are implicated in viral clearance; however, their role in hepatitis C virus (HCV) infection remains controversial. Here, iNKT cells were studied during different stages of HCV infection. iNKT cells from patients with acute HCV infection and people who inject drugs (PWID) with chronic or spontaneously resolved HCV infection were characterized by flow cytometry. In a longitudinal analysis during acute HCV infection, frequencies of activated CD38+ iNKT cells reproducibly declined in spontaneously resolving patients, whereas they were persistently elevated in patients progressing to chronic infection. During the first year of infection, the frequency of activated CD38+ or CD69+ iNKT cells strongly correlated with alanine transaminase levels with particularly pronounced correlations in spontaneously resolving patients. Increased frequencies of activated iNKT cells in chronic HCV infection were confirmed in cross-sectional analyses of PWID with chronic or spontaneously resolved HCV infection; however, no apparent functional differences were observed with various stimulation protocols. Our data suggest that iNKT cells are activated during acute hepatitis C and that activation is sustained in chronic infection. The correlation between the frequency of activated iNKT cells and alanine transaminase may point toward a role of iNKT cells in liver damage.
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ADP-Ribosil Ciclasa 1/análisis , Antígenos CD/análisis , Antígenos de Diferenciación de Linfocitos T/análisis , Hepacivirus , Hepatitis C , Lectinas Tipo C/análisis , Activación de Linfocitos/inmunología , Células T Asesinas Naturales , Enfermedad Aguda , Alanina Transaminasa/sangre , Estudios Transversales , Hepacivirus/aislamiento & purificación , Hepacivirus/patogenicidad , Hepacivirus/fisiología , Hepatitis C/sangre , Hepatitis C/fisiopatología , Hepatitis C/virología , Humanos , Células T Asesinas Naturales/inmunología , Células T Asesinas Naturales/virología , Infección Persistente/inmunología , Infección Persistente/virología , Remisión Espontánea , Carga Viral/inmunologíaRESUMEN
Currently, there are no curative treatment options for mycosis fungoides (MF) and Sézary syndrome (SS) other than stem cell transplant. Understanding the interplay between tumor cells and tumor microenvironment could aid in the development of new therapies. Tumor-associated macrophages (TAMs) mostly have M2 phenotype that promotes tumor progression. This study investigated CD68+ and CD163+ TAMs as well as CD163/CD68 ratio in skin lesions from different stages of MF, large-plaque parapsoriasis, and SS. Moreover, we analyzed serum levels of sCD163 and CCL22 in correlation with TAMs count and CD163/CD68 ratio. CD68+ and CD163+ TAMs count significantly increased as the disease progressed. CD163/CD68 ratio was highest at MF tumor stage and SS indicating M2 polarization with disease progression. Significant positive correlations were detected between serum levels of sCD163 and CCL22 and CD68+ and CD163+ TAMs count and CD163/CD68 ratio. We concluded that TAMs play an important role in MF progression. High CD163/CD68 ratio in tumor stage MF and SS indicates M2 polarization of TAMs with tumor progression. CD163/CD68 ratio should be considered in assessing TAMs rather than total TAMs count. Also, sCD163 and CCL22 serum levels reflect M2 load and thus could be used as markers to assess disease progression.
Asunto(s)
Antígenos CD/análisis , Antígenos de Diferenciación Mielomonocítica/análisis , Quimiocina CCL22/sangre , Micosis Fungoide/patología , Receptores de Superficie Celular/análisis , Síndrome de Sézary/patología , Macrófagos Asociados a Tumores/patología , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Piel/patologíaRESUMEN
The tight junction membrane protein claudin 1 and the adherens junction protein E-cadherin play critical roles in cell-cell communication and in cell signaling. As a result, their protein levels and distribution in cancer have been a focus of cancer researchers in recent years. The loss of sensitivity to contact inhibition and the establishment of invasive properties in cancer are thought to be a result of the mislocalization of these membrane proteins to the cytoplasm. However, reports on their distribution and levels have been inconsistent. It is therefore critical that the techniques used to determine the cellular localization of these proteins be both consistent and reliable. This study was undertaken to determine the optimal fixation method, methanol or formalin, for the detection of claudin 1 and E-cadherin by immunofluorescence in five different human breast cancer cell lines. Both methods exhibited staining of the cell membrane and cytoplasm, but the strongest and most distinct signals were obtained using methanol fixation. Interestingly, cell-specific differences were also observed that appeared to be associated with levels of claudin 1 and E-cadherin as seen by Western blotting. Therefore, when evaluating cellular localization of the junction proteins claudin 1 and E-cadherin, expression level and cell type differences must be considered.
Asunto(s)
Antígenos CD/análisis , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/diagnóstico , Cadherinas/análisis , Western Blotting , Línea Celular , Femenino , Humanos , Microscopía FluorescenteRESUMEN
DISEASE OVERVIEW: Hairy cell leukemia (HCL) and HCL-like disorders, including HCL variant (HCL-V) and splenic diffuse red pulp lymphoma (SDRPL), are a very heterogeneous group of mature lymphoid B-cell disorders characterized by the identification of hairy cells, a specific genetic profile, a different clinical course, and the need for appropriate treatment. DIAGNOSIS: Diagnosis of HCL is based on morphological evidence of hairy cells, an HCL immunologic score of 3 or 4 based on the CD11C, CD103, CD123, and CD25 expression, the trephine biopsy which makes it possible to specify the degree of tumoral medullary infiltration and the presence of BRAFV600E somatic mutation. RISK STRATIFICATION: Progression of patients with HCL is based on a large splenomegaly, leukocytosis, a high number of hairy cells in the peripheral blood, and the immunoglobulin heavy chain variable region gene mutational status. VH4-34-positive HCL cases are associated with a poor prognosis. TREATMENT: Patients should be treated only if HCL is symptomatic. Chemotherapy with risk adapted therapy purine analogs (PNAs) are indicated in first-line HCL patients. The use of chemo-immunotherapy combining PNAs and rituximab (R) represents an increasingly used therapeutic approach. Management of relapsed/refractory disease is based on the use of BRAF inhibitors (BRAFi) plus rituximab or MEK inhibitors (MEKi), recombinant immunoconjugates targeting CD22 or Bruton Tyrosine Kinase inhibitors (BTKi). However, the optimal sequence of the different treatments remains to be determined. The Bcl2-inhibitors (Bcl-2i) can play a major role in the future.