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1.
Tuberk Toraks ; 69(2): 133-143, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34256503

RESUMO

Introduction: The aim of this study was to evaluate the predictive power of LENT (LDH in pleural fluid, Eastern Cooperative Oncology Group [ECOG] performance status, neutrophil-lymphocyte ratio in the serum, and tumor type) score which is a current prognostic score in patients with MPE and to determine its effect on survival and its status in clinical decision making. In addition, it was aimed to compare LENT score with the conventional but subjective score ECOG. Materials and Methods: A retrospective observational study was conducted reviewing the medical records of patients managed for MPE (malign pleural effusion) between 2008 and 2018. LENT prognostic score was calculated in the patients. The ECOG score calculated for the same patients was compared in terms of mortality. Result: A total of 191 patients with malignant pleural effusion, 118 males (61.7%) and 73 females (38.2%), were included in the study. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for identifying overall survival were 69.8 %, 100%, 100% and 18.8%, respectively at the LENT score > 4 (p= 0.000). At ECOG PS >2, the sensitivity, specificity, PPV, NPV were as the same as the LENT score >4 for identifying overall survival. In all patients, overall median survival according to the LENT score was 662/119/33 days in low/moderate/high risk groups, respectively. Cox regression analysis indicated that having a moderate LENT score (p= 0.004, OR: 2.21, CI: 1.29 -3.78%) and high LENT score (p= 0.000, OR: 4, 50 CI: 2.57-7.89%) were predictors for overall survival in all patients due to MPE. In ROC analysis, there was no difference in mortality in erms of both LENT and ECOG at 1st, 6th and 12th months. Conclusions: LENT is a better scoring system than ECOG in predicting early mortality, while both ECOG and LENT have almost the same power in predicting mortality. However, LENT is slightly more objective but more difficult to calculate because it contains laboratory findings. Thus, both scoring systems can be used to predict mortality in patients with malignant pleural effusions. Neither of them has superiority to each other.


Assuntos
Derrame Pleural Maligno/patologia , Adulto , Idoso , Biomarcadores/sangue , Feminino , Humanos , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/patologia , Derrame Pleural Maligno/sangue , Prognóstico , Curva ROC
2.
Acta Cytol ; 65(4): 348-353, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34077933

RESUMO

INTRODUCTION: Multiplex biomarker analysis of cytological body fluid specimens is often used to assist cytologists in distiguishing metastatic cancer cells from reactive mesothelial cells. However, evaluating biomarker expression visually may be challenging, especially when the cells of interest are scant. Deep-learning algorithms (DLAs) may be able to assist cytologists in analyzing multiple biomarker expression at the single cell level in the multiplex fluorescence imaging (MFI) setting. This preliminary study was performed to test the feasibility of using DLAs to identify immunofluorescence-stained metastatic adenocarcinoma cells in body fluid cytology samples. METHODS: A DLA was developed to analyze MFI-stained cells in body fluid cytological samples. A total of 41 pleural fluid samples, comprising of 20 positives and 21 negatives, were retrospectively collected. Multiplex immunofluorescence labeling for MOC31, BerEP4, and calretinin, were performed on cell block sections, and results were analyzed by manual analysis (manual MFI) and DLA analysis (MFI-DLA) independently. RESULTS: All cases with positive original cytological diagnoses showed positive results either by manual MFI or MFI-DLA, but 2 of the 14 (14.3%) original cytologically negative cases had rare cells with positive MOC31 and/or BerEP4 staining in addition to calretinin. Manual MFI analysis and MFI-DLA showed 100% concordance. CONCLUSION: MFI combined with DLA provides a potential tool to assist in cytological diagnosis of metastatic malignancy in body fluid samples. Larger studies are warranted to test the clinical validity of the approach.


Assuntos
Adenocarcinoma/química , Biomarcadores Tumorais/análise , Citodiagnóstico , Aprendizado Profundo , Diagnóstico por Computador , Imunofluorescência , Processamento de Imagem Assistida por Computador , Microscopia de Fluorescência , Derrame Pleural Maligno/química , Adenocarcinoma/secundário , Diagnóstico Diferencial , Estudos de Viabilidade , Humanos , Derrame Pleural Maligno/patologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos
3.
Medicine (Baltimore) ; 100(19): e25748, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34106603

RESUMO

ABSTRACT: The British Thoracic Society guidelines recommend observation for patients with asymptomatic malignant pleural effusion (MPE). However, asymptomatic MPE can become symptomatic. This study examined the clinical course of asymptomatic MPE in patients with non-small cell lung cancer (NSCLC), including the incidence and timing of symptom development of asymptomatic MPE and the associated factors.Retrospective data of 4822 NSCLC patients between January 2012 and December 2017 were reviewed. Symptom development of asymptomatic MPE was defined as the development of symptoms requiring additional treatment, such as insertion of a chest tube, within 1 year in patients who lacked MPE symptoms at the time of diagnosis. Clinical information, pathological parameters, and radiological characteristics were reviewed. Patient data up to 1 year from the initial diagnosis were reviewed.Of 113 patients with asymptomatic MPE, 46 (41%) became symptomatic within 1 year despite appropriate anticancer treatment. The median time to symptom development was 4 months, and 38 patients (83%) developed symptoms within 6 months. Multivariate logistic regression showed that female sex (odds ratio [OR], 0.256; 95% confidence interval [CI], 0.101-0.649; P = .004) and the depth of pleural effusion on initial computed tomography (CT) (OR, 0.957; 95% CI, 0.932-0.982; P = .001) were independently associated with symptom development of asymptomatic MPE.A fraction of 41% of patients with asymptomatic MPE became symptomatic within 1 year. Female sex and larger MPE on initial CT were independently associated with symptom development of asymptomatic MPE.


Assuntos
Adenocarcinoma/complicações , Carcinoma Pulmonar de Células não Pequenas/complicações , Neoplasias Pulmonares/complicações , Derrame Pleural Maligno/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Assintomáticas , Progressão da Doença , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Derrame Pleural Maligno/epidemiologia , Derrame Pleural Maligno/etiologia , Derrame Pleural Maligno/patologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X
4.
J Leukoc Biol ; 110(1): 39-52, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33847412

RESUMO

IL-26 is a newly discovered IL-10 cytokine family member mainly secreted by Th17 cells. However, the relationship between IL-26 and lung cancer remains unclear. The present study reported that IL-26 is involved in the production and promotion of malignant pleural effusion (MPE) for the first time. The concentrations of IL-26 and several Th17-related cytokines in MPE and peripheral blood (PB) from MPE patients were measured. IL-26, IL-10, and IL-6 were elevated in MPE compared to PB. The cell resource of IL-26 was primary Th17 cells measured by flow cytometry, whereas Tc17 cells and macrophages could also contribute to higher concentration of IL-26 in MPE. Abundant IL-6 and IL-23 in MPE could promote the frequency of IL-26 expressed by CD4+ T cells through phosphorylating STAT3 signaling pathway and promoting the expression of a specific Th17 lineage marker RORγt subsequently. IL-26 could selectively increase Th22 proportion through up-regulating the percentage of Ki-67 expressed by CD4+ T cells and the expression of IL-22 secreted by memory CD4+ T cells. In addition, IL-26 could decrease secretion of granzyme B. The tumor-killing activity of CD8+ T cells were inhibited as well when cocultured with malignant cells. Furthermore, the accumulation of IL-26 protein in MPE predicted poor patient survival. In summary, our results indicated that IL-26 was involved in the pathogenesis of MPE by exerting its impacts on both CD4+ T cells and CD8+ T cells.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Interleucinas/metabolismo , Derrame Pleural Maligno/etiologia , Derrame Pleural Maligno/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Biomarcadores , Diferenciação Celular/imunologia , Citocinas/metabolismo , Citotoxicidade Imunológica , Humanos , Ativação Linfocitária , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Derrame Pleural Maligno/patologia
5.
PLoS One ; 16(4): e0250628, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33901252

RESUMO

Predicting survival of patients with malignant pleural effusions (MPEs) is notoriously difficult. A robust prognostic marker can guide clinical decision making. The neutrophil-to-lymphocyte ratio (NLR) in blood has been shown to predict survival in many cancers. Pleural fluid bathes the malignant pleural tissues, thus the NLR of the pleural fluid may reflect more closely the local tumour environment. The objective of this study was to explore the prognostic significance of pleural effusion NLR for MPE. We analysed matched effusion and blood from 117 patients with malignant and 24 with benign pleural effusions. Those who had received recent chemotherapy or had a pleurodesis were excluded. Neutrophil and lymphocyte counts in effusions were performed by manual review of cytospin cell preparations by trained observers. Clinical data were extracted from a state-wide hospital database. We found significantly fewer neutrophils (expressed as percentage of total leukocyte count) in pleural fluid than in corresponding blood (9% vs 73%; p<0.001). The NLR was an order of magnitude lower in pleural fluid than in corresponding blood: median [IQR] = 0.20 [0.04-1.18] vs 4.9 [3.0-8.3], p<0.001. Correlation between blood and pleural fluid NLR in MPE patients was moderate (rs = 0.321, p<0.001). In univariate analysis, NLR (>0.745)) in malignant pleural fluid was predictive of poorer survival (HR = 1.698 [1.0054-2.736]; p = 0.030), and remained significant after adjustment for age, sex, presence of a chest drain, cancer type, concurrent infection and subsequent treatment with chemotherapy (HR = 1.786 [1.089-2.928]; p = 0.022). Patients with pleural fluid NLR > 0.745 had a significantly shorter median survival of 130 (95% CI 0-282) days compared to 312 (95% CI 195-428) days for pleural NLR < 0.745, p = 0.026. The NLR in blood was also predictive of poorer survival in MPE patients (HR = 1.959 [1.019-3.096]; p<0.001). The proportion of neutrophils in pleural fluid was predictive of prognosis more strongly than lymphocytes. This study provides evidence that NLR in malignant effusions can predict survival, and therefore may provide prognostic information for this cohort. This prognostic association in the fluid is driven by the presence of neutrophils.


Assuntos
Linfócitos/citologia , Neutrófilos/citologia , Derrame Pleural Maligno/patologia , Idoso , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Derrame Pleural Maligno/mortalidade , Prognóstico , Modelos de Riscos Proporcionais , Taxa de Sobrevida
6.
Cancer Med ; 10(7): 2286-2292, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33656807

RESUMO

BACKGROUND: Pleural effusion from patients with advanced non-small cell lung cancer (NSCLC) has been proved valuable for molecular analysis, especially when the tissue sample not available. However, simultaneous detection of multiple driver gene alterations especially the fusions is still challenging. METHODS: In this study, 77 patients with advanced NSCLC and pleural effusion were enrolled, 49 of whom had matched tumor tissues. Supernatants, cell sediments, and cell blocks were prepared from pleural effusion samples for detection of driver alterations by a PCR-based 9-gene mutation detection kit. RESULTS: Mutations in EGFR, KRAS, and HER2 were detected in DNA and cfDNA, fusions in ALK was detected in RNA and cfRNA. Compared with matched tumor tissue, the supernatant showed the highest overall sensitivity (81.3%), with 81.5% for SNV/Indels by cfDNA and 80% for fusions by cfRNA, followed by cell blocks (71.0%) and the cell sediments (66.7%). Within the group of treatment-naïve patients or malignant cells observed in the cell sediments, supernatant showed higher overall sensitivity (89.5% and 92.3%) with both 100% for fusions. CONCLUSIONS: CfDNA and cfRNA derived from pleural effusion supernatant have been successfully tested with a PCR-based multigene detection kit. Pleural effusion supernatant seems a preferred material for detection of multigene alterations to guide treatment decision of advanced NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Ácidos Nucleicos Livres/genética , Fusão Gênica , Neoplasias Pulmonares/genética , Mutação , Derrame Pleural Maligno/genética , Quinase do Linfoma Anaplásico/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , DNA de Neoplasias , Feminino , Genes erbB-1 , Genes erbB-2 , Genes ras , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Derrame Pleural Maligno/patologia , Reação em Cadeia da Polimerase/métodos , Sensibilidade e Especificidade
7.
Int J Oncol ; 58(3): 359-370, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33650668

RESUMO

Patients with a variety of malignancies can develop malignant pleural effusion (MPE). MPE can cause significant symptoms and result in a marked decrease in quality of life and a poor prognosis. MPE is primarily considered as an immune and vascular manifestation of pleural metastases. In the present review, the existing evidence supporting the applicability of anti­angiogenic therapy and immunotherapy for the treatment of MPE was summarized. Patients with MPE have benefited from anti­angiogenic agents, including bevacizumab and endostar; however, no relevant prospective phase III trial has, thus far, specifically analyzed the benefit of anti­angiogenic therapy in MPE. Immunotherapy for MPE may be sufficient to turn a dire clinical situation into a therapeutic advantage. Similar to anti­angiogenic therapy, more clinical data on the efficiency and safety of immunotherapy for controlling MPE are urgently required. The combined use of anti­angiogenic therapy and immunotherapy may be a promising strategy for MPE, which requires to be further understood.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Imunoterapia/métodos , Terapia Viral Oncolítica/métodos , Derrame Pleural Maligno/terapia , Bevacizumab/uso terapêutico , Vacinas Anticâncer/administração & dosagem , Terapia Combinada/métodos , Células Dendríticas/imunologia , Endostatinas/uso terapêutico , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Cavidade Pleural/efeitos dos fármacos , Cavidade Pleural/imunologia , Cavidade Pleural/patologia , Derrame Pleural Maligno/imunologia , Derrame Pleural Maligno/mortalidade , Derrame Pleural Maligno/patologia , Prognóstico , Qualidade de Vida , Proteínas Recombinantes/uso terapêutico , Evasão Tumoral
8.
Acta Cytol ; 65(3): 235-241, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33631757

RESUMO

PURPOSE: For anaplastic lymphoma kinase (ALK) gene detection, the centrifugal sedimentation method (CSM) and cell block method (CBM) are commonly used to process samples of bloody pleural effusions (BPEs). However, in practice, the impurity content in the processed samples often affects the results and even leads to the detection failure. The purpose of this study was to establish a cell enrichment method (CEM) by using a disposable membrane cell collector to remove blood and inflammatory cells and enrich lung adenocarcinoma cells in BPE for more efficient RNA extraction and ALK gene detection. MATERIALS AND METHODS: CEM proposed in this study and the traditional CSM and CBM were used to treat BPE samples collected from 37 lung adenocarcinoma patients. A DeNovix DS-11 ultraviolet spectrophotometer was used to measure the concentration and purity of extracted RNA. Amplification refractory mutation systems (ARMS) and ABI 7500 fluorescence qPCR were used to detect ALK gene. Through statistical analysis, the CEM was compared with the CSM and CBM in RNA concentration, purity, and ALK gene detection results. RESULTS: The concentration of RNA extracted by using the CEM was significantly higher than that extracted by using the CBM and CSM (p < 0.001). The purity of RNA extracted by using the CEM was significantly higher than that by the other 2 methods (p = 0.011, p = 0.005). ALK gene testing with PCR was successful in all the samples using the CEM, but 2 cases by the CSM and 1 case by the CBM failed. CONCLUSIONS: Using the disposable membrane cell collector to process BPE of lung adenocarcinoma patients for RNA extraction and ALK gene detection is more effective and successful compared with the traditional methods, and it is suggested to be further applied and popularized in clinical practice.


Assuntos
Adenocarcinoma de Pulmão/genética , Quinase do Linfoma Anaplásico/genética , Biomarcadores Tumorais/genética , Separação Celular/instrumentação , Equipamentos Descartáveis , Fusão Gênica , Neoplasias Pulmonares/genética , Membranas Artificiais , Derrame Pleural Maligno/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adenocarcinoma de Pulmão/enzimologia , Adenocarcinoma de Pulmão/patologia , Centrifugação , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/patologia , Inclusão em Parafina , Derrame Pleural Maligno/sangue , Derrame Pleural Maligno/enzimologia , Derrame Pleural Maligno/patologia , Valor Preditivo dos Testes , Fixação de Tecidos
9.
Int J Med Sci ; 18(6): 1510-1518, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33628109

RESUMO

Cell-free DNA (cfDNA) in supernatant of pleural effusion from advanced NSCLC patients has been proved as surrogate sample detecting therapeutic targets as well as tumor mutation burden (TMB). As recently reported, cfDNA in pleural effusion supernatant is superior to plasma in TMB evaluation. It is reasonable to hypothesize that cfDNA profile in pleural effusion (PE) and plasma might be different. It remains to be elucidated why cfDNA in PE supernatant impacts on genetic analysis. Consequently, the approach dealing with cfDNA from PE supernatant might need to be different from that for plasma cfDNA in order to obtain accurate clinical genetic testing result. Methods: Pleural effusion samples from 32 patients with stage IV lung adenocarcinoma were collected. Supernatant and sediment were processed separately to extract Cell-free DNA as well as sediment DNA (PE-S). cfDNA from pleural effusion was analyzed by Agilent 2100 bioanalyzer. Libraries were prepared by 1) direct use of the total cfDNA without fragmentation step (PE-FL) or 2) use of full-length cfDNA fragmented to 150-250bp (PE-F), 3) use of cfDNA fragments enriched to ~167bp (PE-E167) as well as 4) use of cfDNA fragments larger than 500bp enriched (PE-E500). All samples were subjected to targeted next-generation sequencing (NGS) with a panel of 448 cancer-related genes as well as a panel of 10 NSCLC driver genes. Results: cfDNA were successfully extracted from 30 MPE samples. cfDNA displayed distinct profile in supernatant of malignant pleural effusion from that of plasma cfDNA. No statistical difference in detection of hotspot variations between PE-E167 and PE-F by 448-gene or 10-gene panel. While TMB from PE-F samples was significantly higher than that from PE-E167 and PE-FL. Higher TMB from PE-F was resulted from cancer-unspecific variants with low allele frequency (0.1%-1%) which were mainly introduced by long-fragment cfDNA. Similar genetic profile was observed between paired cfDNA of PE-FL and cfDNA of PE-E167. Conclusion: Long-fragment cfDNA in the PE supernatant will introduce low abundant cancer unrelated variants which leads overestimation of TMB. Paired PE-FL and PE-E167 gave comparable outcomes. Direct use of the total cfDNA without fragmentation step (PE-FL) is recommended for library preparation of NGS testing in clinical practice to exclude interference from long fragments of the cfDNA.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Ácidos Nucleicos Livres/análise , Testes Genéticos/estatística & dados numéricos , Neoplasias Pulmonares/diagnóstico , Derrame Pleural Maligno/patologia , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/genética , Ácidos Nucleicos Livres/genética , Erros de Diagnóstico/estatística & dados numéricos , Feminino , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/genética
10.
Ecotoxicol Environ Saf ; 208: 111618, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396138

RESUMO

Air pollution has been recognized to be a risk factor for lung cancer. The objective of this study was to investigate the effects of air pollution on heavy metal alterations in the pleural effusion of lung cancer patients. Pleural effusion was collected from patients with lung cancer and congestive heart failure (CHF). One-year average levels of particulate matter with an aerodynamic diameter of < 10 µm (PM10), PM2.5, NO2, and SO2 were linked to the exposure of these subjects. Traffic-related metals, included Al, Fe, Cu, Zn, and Pb, were determined in the pleural effusion. Logistic regression models were used to examine their associations. There were 63 lung cancer patients and 31 CHF patients enrolled in the current study. We found that PM10, PM2.5, and NO2 were negatively correlated with Al in the pleural effusion, whereas PM2.5 was positively correlated with Zn in the pleural effusion. Increases in 1 µg/m3 of PM2.5 and 1 ng/mL of Zn were associated with lung cancer (adjusted OR=2.394, 95% CI= 1.446-3.964 for PM2.5; adjusted OR=1.003, 95% CI=1.000-1.005 for Zn). Increases in PM2.5 and Zn in the pleural effusion increased the risk of malignant pleural effusion in lung cancer patients (adjusted OR=1.517; 95% CI=1.082-2.127 for PM2.5; adjusted OR=1.002, 95% CI=1.000-1.005 for Zn). Furthermore, we observed that adenocarcinomas increased in association with a 1-µg/m3 increase in PM2.5 (crude OR=1.683; 95% CI=1.006-2.817) in lung cancer patients. In conclusion, PM2.5 exposure and the possible resultant Zn in the pleural effusion associated with the development of malignant pleural effusion in lung cancer.


Assuntos
Poluentes Atmosféricos/análise , Exposição Ambiental/análise , Neoplasias Pulmonares/epidemiologia , Metais Pesados/análise , Material Particulado/análise , Derrame Pleural Maligno/epidemiologia , Idoso , Poluentes Atmosféricos/toxicidade , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Metais Pesados/toxicidade , Pessoa de Meia-Idade , Tamanho da Partícula , Material Particulado/toxicidade , Derrame Pleural Maligno/química , Derrame Pleural Maligno/patologia , Fatores de Risco , Taiwan
11.
Cancer Cytopathol ; 129(6): 468-478, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33493383

RESUMO

BACKGROUND: Malignant mesothelioma (MM) is a therapy-resistant tumor, often causing an effusion. Drugs targeting the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway have shown promising results, but assessment of PD-L1 expression to select patients for therapy has mainly been performed on histologic tissue samples. In a previous study, we showed that MM effusions are suitable for PD-L1 assessment with results comparable to those reported in histologic studies, but no studies have compared PD-L1 expression in histologic and cytologic samples. METHODS: PD-L1 expression was determined immunohistochemically (clone 28-8) in 61 paired samples of effusions and biopsies from patients with pleural MM, obtained at the time of diagnosis. Only cases with >100 tumor cells were included. Membranous staining in tumor cells was considered positive at ≥1%, >5%, >10%, and >50% cutoff levels. RESULTS: Of 61 histologic samples, PD-L1 expression was found in 28 and 7 samples at ≥1% and >50% cutoffs, respectively; the corresponding figures for cytology were 21 and 5, respectively. The overall percentage agreement between histology and cytology was 69% and 84%, with a kappa (κ) of 0.36 and 0.08 at ≥1% and >50% cutoffs, respectively. The concordance between cytology and histology tended to be higher for epithelioid MM versus nonepithelioid MM at a ≥1% cutoff. PD-L1 positivity in biopsies, but not in effusions, correlated with the histologic subtype at a ≥1% cutoff. CONCLUSIONS: A moderate concordance of PD-L1 expression between biopsies and effusions from pleural MM, especially for the epithelioid subtype, indicates biological differences between the 2 types of specimens. Cytology and histology may be complementary.


Assuntos
Antígeno B7-H1/metabolismo , Células Epitelioides/patologia , Mesotelioma/patologia , Derrame Pleural Maligno/patologia , Neoplasias Pleurais/patologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Citodiagnóstico/métodos , Células Epitelioides/metabolismo , Feminino , Seguimentos , Humanos , Masculino , Mesotelioma/metabolismo , Mesotelioma/cirurgia , Pessoa de Meia-Idade , Derrame Pleural Maligno/metabolismo , Derrame Pleural Maligno/cirurgia , Neoplasias Pleurais/metabolismo , Neoplasias Pleurais/cirurgia , Prognóstico
12.
Cancer Sci ; 112(5): 2006-2019, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33484069

RESUMO

Liquid biopsy analyzes the current status of primary tumors and their metastatic regions. We aimed to develop an optimized protocol for single-cell sequencing of floating tumor cells (FTCs) in pleural effusion as a laboratory test. FTCs were enriched using a negative selection of white blood cells by a magnetic-activated cell sorting system, and CD45-negative and cytokeratin-positive selection using a microfluidic cell separation system with a dielectrophoretic array. The enriched tumor cells were subjected to whole-genome amplification (WGA) followed by genome sequencing. The FTC analysis detected an EGFR exon 19 deletion in Case 1 (12/19 cells, 63.2%), and EML4-ALK fusion (17/20 cells, 85%) with an alectinib-resistant mutation of ALK (p.G1202R) in Case 2. To eliminate WGA-associated errors and increase the uniformity of the WGA product, the protocol was revised to sequence multiple single FTCs individually. An analytical pipeline, accurate single-cell mutation detector (ASMD), was developed to identify somatic mutations of FTCs. The large numbers of WGA-associated errors were cleaned up, and the somatic mutations detected in FTCs by ASMD were concordant with those found in tissue specimens. This protocol is applicable to circulating tumor cells analysis of peripheral blood and expands the possibility of utilizing molecular profiling of cancers.


Assuntos
Perfilação da Expressão Gênica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Biópsia Líquida/métodos , Derrame Pleural Maligno/genética , Derrame Pleural Maligno/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quinase do Linfoma Anaplásico/genética , Antineoplásicos/uso terapêutico , Carbazóis/farmacologia , Separação Celular/métodos , Crizotinibe/uso terapêutico , DNA/isolamento & purificação , Resistencia a Medicamentos Antineoplásicos/genética , Éxons/genética , Feminino , Amplificação de Genes , Deleção de Genes , Genes erbB-1 , Humanos , Separação Imunomagnética/métodos , Queratinas , Antígenos Comuns de Leucócito , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Células Neoplásicas Circulantes , Proteínas de Fusão Oncogênica/genética , Piperidinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia
13.
Adv Anat Pathol ; 28(2): 94-104, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33229932

RESUMO

Lymphocyte-rich effusions of the body cavities may represent a reactive/benign condition, primary effusion lymphoma, or systemic lymphoma with secondary malignant effusion, either as initial presentation or as a late complication. Cytomorphologic examination is essential and fundamental for diagnosis and may provide important clues to the nature of diseases. However, based on morphology alone, cytologic diagnosis of lymphocyte-rich effusions could be very challenging, particularly when the lymphocytes are small. Cytologists/cytopathologists might be uncertain when a lymphocyte-rich effusion specimen warrants a comprehensive hematopathologic workup. Herein we present a simple and practical algorithmic approach. On the basis of the cytomorphology of lymphocytes (small vs. large cells), presence or absence of cellular atypia, and clinical information (an earlier history or current lymphoma), the lymphocyte-rich effusion samples could be triaged for ancillary studies including immunophenotyping and molecular assays if indicated. Incorporation of cytomorphology, correlation with clinical information, and appropriate application of various ancillary techniques is mandatory for a correct diagnosis of lymphocyte-rich effusion specimens.


Assuntos
Linfócitos/patologia , Linfoma/patologia , Derrame Pleural Maligno/patologia , Humanos , Imunofenotipagem , Linfoma/diagnóstico , Derrame Pleural Maligno/diagnóstico
14.
Cancer Lett ; 500: 21-28, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33309856

RESUMO

Malignant pleural effusion (MPE) is a frequent complication of malignancies and poses a clinical problem. CD4+ T lymphocytes are the most frequent cell population in MPE. Traditionally, CD4+ T cells are classified into two subsets based on cytokine production profiles, type 1 (Th1) and type 2 (Th2) helper T cells, which exhibit distinct functions. Recently, other T-cell subsets have been added to the Th-cell "portfolio", including regulatory T, Th17, Th9, and Th22 cells. The current review focuses on summarizing the Th-cell phenotypic characteristics, mechanism of Th-cell differentiation, and their pleural space recruitment, based on recent research. We also describe the interplay in MPE among different Th cells, as well as Th cells and lung cancer cells or mesothelial cells. Future research should expand the landscape map of human MPE immune cells, explore the immuno-regulation of B cells, and investigate the communication between macrophages and Th cells in MPE, which may facilitate meaningful advancements in the diagnoses and therapeutics of MPE.


Assuntos
Derrame Pleural Maligno/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Reguladores/imunologia , Células A549 , Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Diferenciação Celular/genética , Humanos , Interleucina-17/genética , Ativação Linfocitária/imunologia , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/genética , Derrame Pleural Maligno/patologia , Transdução de Sinais/genética , Células Th1/imunologia , Células Th17/imunologia
15.
Cancer Sci ; 112(2): 781-791, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33315285

RESUMO

Malignant pleural effusion is a common complication in metastatic breast cancer (MBC); however, changes in the pleural microenvironment are poorly characterized, especially with respect to estrogen receptor status. Histologically, MBC presents with increased microvessels beneath the parietal and visceral pleura, indicating generalized angiogenic activity. Breast cancer-associated pleural fluid (BAPF) was collected and cultured with HUVECs to recapitulate the molecular changes in subpleural endothelial cells. The clinical progression of triple-negative breast cancer (TNBC) is much more aggressive than that of hormone receptor-positive breast cancer (HPBC). However, BAPF from HPBC (BAPF-HP) and TNBC (BAPF-TN) homogeneously induced endothelial proliferation, migration, and angiogenesis. In addition, BAPF elicited negligible changes in the protein marker of endothelial-mesenchymal transition. Both BAPF-HP and BAPF-TN exclusively upregulated JNK signaling among all MAPKs in HUVECs. By contrast, the response to the JNK inhibitor was insignificant in Transwell and tube formation assays of the HUVECs cultured with BAPF-TN. The distinct contribution of p-JNK to endothelial angiogenesis was consequently thought to be induced by BAPF-HP and BAPF-TN. Due to increased angiogenic factors in HUVECs cultured with BAPF, vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor was applied accordingly. Responses to VEGFR2 blockade were observed in both BAPF-HP and BAPF-TN concerning endothelial migration and angiogenesis. In conclusion, the above results revealed microvessel formation in the pleura of MBC and the underlying activation of p-JNK/VEGFR2 signaling. Distinct responses to blocking p-JNK and VEGFR2 in HUVECs cultured with BAPF-HP or BAPF-TN could lay the groundwork for future investigations in treating MBC based on hormone receptor status.


Assuntos
Neoplasias da Mama/patologia , Sistema de Sinalização das MAP Quinases/fisiologia , Neovascularização Patológica/metabolismo , Derrame Pleural Maligno/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Idoso , Neoplasias da Mama/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Neovascularização Patológica/patologia , Derrame Pleural Maligno/patologia
16.
Zhongguo Fei Ai Za Zhi ; 23(12): 1080-1086, 2020 Dec 20.
Artigo em Chinês | MEDLINE | ID: mdl-33357315

RESUMO

BACKGROUND: Malignant plural effusion (MPE) is one of the most common specimen for liquid biopsy gene detection. This study aims to explore a method for isolating tumor cells from large volume of MPE and evaluate its efficacy and application prospect in gene detection. METHODS: Pleural effusions (>500 mL) from 20 advanced lung cancer patients were obtained by effusion drainage and used to isolate tumor cells with cell separation media Percoll and Ficoll. Cell number and purity were calculated. DNA was extracted from the supernatant (etDNA), total cells and isolated tumor cells of pleural effusion (ETC-DNA) to detect the mutation of tumor-related genes by next-generation sequencing. RESULTS: The median number of cells isolated from malignant pleural effusion was 8.50×104 (interquel range: 9.25×10³-3.75×105), 85.50%±5.80% of the cells were identified as tumor cells. The detection rates of epidermal growth factor receptor (EGFR) gene mutation of etDNA, total cell DNA and ETC-DNA were 70.00%, 50.00% and 70.00%, reseparately, while the median EGFR mutation abundance in 3 components was 16.05% (4.78%-43.06%), 1.09% (0.00%-2.39%), and 33.02% (18.50%-76.70%), respectively. ETC-DNA had good consistency with tissue DNA (P>0.999, kappa=1.000) and etDNA (P>0.999, kappa=1.000). ETC-DNA inclined to have higher EGFR mutation than etDNA, but the result was not statistically significant. CONCLUSIONS: Our method can isolate large amount of tumor cells from a large volume of malignant pleural effusion with high purity. Using ETC-DNA as specimen improves the efficacy of gene detection, thus is worth further study.


Assuntos
Separação Celular/métodos , Derrame Pleural Maligno/patologia , Idoso , Receptores ErbB/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Derrame Pleural Maligno/genética , Fatores de Tempo
17.
J Immunol ; 205(10): 2926-2935, 2020 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-33046503

RESUMO

Emerging evidence indicates that Myo9b is a cancer metastasis-related protein and functions in a variety of immune-related diseases. However, it is not clear whether and how Myo9b functions in malignant pleural effusion (MPE). In this study, our data showed that Myo9b expression levels correlated with lung cancer pleural metastasis, and nucleated cells in MPE from either patients or mice expressed a lower level of Myo9b than those in the corresponding blood. Myo9b deficiency in cancer cells suppressed MPE development via inhibition of migration. Myo9b deficiency in mice suppressed MPE development by decreasing TH1 cells and increasing TH17 cells. CD4+ naive T cells isolated from Myo9b-/- mouse spleens exhibited less TH1 cell differentiation and more TH17 cell differentiation in vitro. mRNA sequencing of nucleated cells showed that T cell-specific adaptor protein (TSAd) was downregulated in Myo9b-/- mouse MPE, and enrichment of the H3K27me3 mark in the TSAd promoter region was found in the Myo9b-/- group. Naive T cells purified from wild type mouse spleens transfected with TSAd-specific small interfering RNAs (siRNAs) also showed less TH1 cell differentiation and more TH17 cell differentiation than those from the siRNA control group. Furthermore, downregulation of TSAd in mice using cholesterol-conjugated TSAd-specific siRNA suppressed MPE development, decreased TH1 cells, and increased TH17 cells in MPE in vivo. Taken together, Myo9b deficiency suppresses MPE development not only by suppressing pleural cancer metastasis but also by regulating TH1/TH17 cell response via a TSAd-dependent pathway. This work suggests Myo9b and TSAd as novel candidates for future basic and clinical investigations of cancer.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias Pulmonares/patologia , Miosinas/metabolismo , Derrame Pleural Maligno/imunologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Biópsia , Linhagem Celular Tumoral/transplante , Modelos Animais de Doenças , Feminino , Técnicas de Silenciamento de Genes , Técnicas de Inativação de Genes , Humanos , Pulmão/patologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/imunologia , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Miosinas/genética , Pleura/patologia , Derrame Pleural Maligno/sangue , Derrame Pleural Maligno/patologia , Transdução de Sinais/imunologia , Células Th1/imunologia , Células Th17/imunologia
18.
Int J Mol Sci ; 21(17)2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32867034

RESUMO

While T cell-based cancer immunotherapies have shown great promise, there remains a need to understand how individual metastatic tumor environments impart local T cell dysfunction. At advanced stages, cancers that metastasize to the pleural space can result in a malignant pleural effusion (MPE) that harbors abundant tumor and immune cells, often exceeding 108 leukocytes per liter. Unlike other metastatic sites, MPEs are readily and repeatedly accessible via indwelling catheters, providing an opportunity to study the interface between tumor dynamics and immunity. In the current study, we examined CD8+ T cells within MPEs collected from patients with heterogeneous primary tumors and at various stages in treatment to determine (1) if these cells possess anti-tumor activity following removal from the MPE, (2) factors in the MPE that may contribute to their dysfunction, and (3) the phenotypic changes in T cell populations that occur following ex vivo expansion. Co-cultures of CD8+ T cells with autologous CD45- tumor containing cells demonstrated cytotoxicity (p = 0.030) and IFNγ production (p = 0.003) that inversely correlated with percent of myeloid derived suppressor cells, lactate, and lactate dehydrogenase (LDH) within the MPE. Ex vivo expansion of CD8+ T cells resulted in progressive differentiation marked by distinct populations expressing decreased CD45RA, CCR7, CD127, and increased inhibitory receptors. These findings suggest that MPEs may be a source of tumor-reactive T cells and that the cellular and acellular components suppress optimal function.


Assuntos
Linfócitos T CD8-Positivos/citologia , Técnicas de Cocultura/métodos , Interferon gama/metabolismo , Neoplasias/patologia , Derrame Pleural Maligno/patologia , Idoso , Idoso de 80 Anos ou mais , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/patologia , Diferenciação Celular , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Subunidade alfa de Receptor de Interleucina-7/metabolismo , L-Lactato Desidrogenase/metabolismo , Ácido Láctico/metabolismo , Antígenos Comuns de Leucócito/metabolismo , Masculino , Pessoa de Meia-Idade , Células Supressoras Mieloides/metabolismo , Células Supressoras Mieloides/patologia , Estadiamento de Neoplasias , Neoplasias/complicações , Neoplasias/imunologia , Derrame Pleural Maligno/etiologia , Derrame Pleural Maligno/imunologia , Receptores CCR7/metabolismo , Células Tumorais Cultivadas
19.
BMC Cancer ; 20(1): 825, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32867726

RESUMO

BACKGROUND: Malignant pleural effusion (MPE) causes substantial symptomatic burden in advanced malignancy. Although pleural fluid cytology is a commonly accepted gold standard of diagnosis, its low diagnostic yield is a challenge for clinicians. The aim of this study was to determine whether pro-cathepsin D can serve as a novel biomarker to discriminate between MPE and benign pleural effusion (BPE). METHODS: This study included 81 consecutive patients with exudative pleural effusions who had underwent thoracentesis or pleural biopsy. Pleural fluid and serum were collected as a standard procedure for all individuals at the same time. The level of pro-cathepsin D was measured by the sandwich enzyme-linked immunosorbent assay method. RESULTS: Though there were no significant differences in plasma pro-cathepsin D between the two groups, the level of pleural fluid pro-cathepsin D was significantly higher in the MPE group than the BPE group (0.651 versus 0.590 pg/mL, P = 0.034). The discriminative power of pleural fluid pro-cathepsin D for diagnosing MPE was moderate, with 81% sensitivity and 53% specificity at a pro-cathepsin D cut-off ≥0.596 pg/mL (area under the curve: 0.656). Positive and negative predictive values for MPE were 38 and 89%, respectively, with pro-cathepsin D cut-off value (> 0.596 pg/mL). CONCLUSIONS: The level of pleural fluid pro-cathepsin D was found to be significantly higher in MPE than in BPE. Although results of this study could not support the sole use of pleural fluid pro-cathepsin D to diagnose MPE, pleural fluid pro-cathepsin D can be added to pre-existing diagnostic methods for ruling-in or ruling-out MPE.


Assuntos
Catepsina D/sangue , Precursores Enzimáticos/sangue , Derrame Pleural Maligno/sangue , Derrame Pleural Maligno/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores Tumorais/sangue , Diagnóstico Diferencial , Ensaio de Imunoadsorção Enzimática , Exsudatos e Transudatos/química , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Derrame Pleural Maligno/patologia , Estudos Retrospectivos
20.
Anticancer Res ; 40(10): 5877-5881, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988918

RESUMO

BACKGROUND/AIM: Pleural effusion (PE) has a heterogeneous aetiology, and differential diagnosis between benign and malignant disease may require invasive procedures in up to 60% of cases. The sensitivity of pleural cytology is limited, and several strategies have been tested to reduce the need of invasive diagnostic approaches. The aim of this study was to evaluate the usefulness of pleural fluid cytology, compared to, and combined with, carcinoembryonic antigen (CEA), C reactive protein (CRP), and lactate dehydrogenase (LDH) assay of pleural fluid (PF) in patients with a history of cancer, exudative non-purulent PE, and suspicion of malignant PE on imaging studies. PATIENTS AND METHODS: The medical records of 40 patients with pulmonary metastases and malignant PE, and 57 controls with benign exudative PE were reviewed. All the patients underwent pleural cytology and CEA, CRP, and LDH assay before VATS-guided biopsy. RESULTS: The sensitivity and specificity were 55.0% and 98.2% (cytology), 35.0% and 98.2% (CEA), 92.5% and 71.9% (CRP), 70.0% and 54.4% (LDH). The multivariate analysis excluded LDH, and the final AUC (cytology+CEA+CRP) was 0.894. CONCLUSION: In all patients with a history of cancer and PE of uncertain origin, the combination of PF cytology plus pleural CEA and CRP assay together should be suggested to recognize malignant plural effusion (MPE), minimising the use of unnecessary invasive investigations.


Assuntos
Diagnóstico Diferencial , Neoplasias/diagnóstico , Pleura/metabolismo , Derrame Pleural Maligno/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Proteína C-Reativa/metabolismo , Antígeno Carcinoembrionário/metabolismo , Citodiagnóstico/métodos , Feminino , Humanos , L-Lactato Desidrogenase/metabolismo , Masculino , Pessoa de Meia-Idade , Neoplasias/metabolismo , Neoplasias/patologia , Pleura/patologia , Derrame Pleural Maligno/metabolismo , Derrame Pleural Maligno/patologia
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