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1.
Pathobiology ; : 1-13, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38527431

RESUMO

INTRODUCTION: Over the past decade, classifications using immune cell infiltration have been applied to many types of tumors; however, mesotheliomas have been less frequently evaluated. METHODS: In this study, 60 well-characterized pleural mesotheliomas (PMs) were evaluated immunohistochemically for the characteristics of immune cells within tumor microenvironment (TME) using 10 immunohistochemical markers: CD3, CD4, CD8, CD56, CD68, CD163, FOXP3, CD27, PD-1, and TIM-3. For further characterization of PMs, hierarchical clustering analyses using these 10 markers were performed. RESULTS: Among the immune cell markers, CD3 (p < 0.0001), CD4 (p = 0.0016), CD8 (p = 0.00094), CD163+ (p = 0.042), and FOXP3+ (p = 0.025) were significantly associated with an unfavorable clinical outcome. Immune checkpoint receptor expressions on tumor-infiltrating lymphocytes such as PD-1 (p = 0.050), CD27 (p = 0.014), and TIM-3 (p = 0.0098) were also associated with unfavorable survival. Hierarchical clustering analyses identified three groups showing specific characteristics and significant associations with patient survival (p = 0.016): the highest number of immune cells (ICHigh); the lowest number of immune cells, especially CD8+ and CD163+ cells (ICLow); and intermediate number of immune cells (ICInt). ICHigh tumors showed significantly higher expression of PD-L1 (p = 0.00038). Cox proportional hazard model identified ICHigh [hazard ratio (HR) = 2.90] and ICInt (HR = 2.97) as potential risk factors compared with ICLow. Tumor CD47 (HR = 2.36), tumor CD70 (HR = 3.04), and tumor PD-L1 (HR = 3.21) expressions were also identified as potential risk factors for PM patients. CONCLUSION: Our findings indicate immune checkpoint and/or immune cell-targeting therapies against CD70-CD27 and/or CD47-SIRPA axes may be applied for PM patients in combination with PD-L1-PD-1 targeting therapies in accordance with their tumor immune microenvironment characteristics.

2.
Cell Mol Life Sci ; 78(8): 4019-4033, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33837451

RESUMO

Epidemiological investigations show that mosaic loss of chromosome Y (LOY) in leukocytes is associated with earlier mortality and morbidity from many diseases in men. LOY is the most common acquired mutation and is associated with aberrant clonal expansion of cells, yet it remains unclear whether this mosaicism exerts a direct physiological effect. We studied DNA and RNA from leukocytes in sorted- and single-cells in vivo and in vitro. DNA analyses of sorted cells showed that men diagnosed with Alzheimer's disease was primarily affected with LOY in NK cells whereas prostate cancer patients more frequently displayed LOY in CD4 + T cells and granulocytes. Moreover, bulk and single-cell RNA sequencing in leukocytes allowed scoring of LOY from mRNA data and confirmed considerable variation in the rate of LOY across individuals and cell types. LOY-associated transcriptional effect (LATE) was observed in ~ 500 autosomal genes showing dysregulation in leukocytes with LOY. The fraction of LATE genes within specific cell types was substantially larger than the fraction of LATE genes shared between different subsets of leukocytes, suggesting that LOY might have pleiotropic effects. LATE genes are involved in immune functions but also encode proteins with roles in other diverse biological processes. Our findings highlight a surprisingly broad role for chromosome Y, challenging the view of it as a "genetic wasteland", and support the hypothesis that altered immune function in leukocytes could be a mechanism linking LOY to increased risk for disease.


Assuntos
Doença de Alzheimer/genética , Cromossomos Humanos Y , Mosaicismo , Neoplasias da Próstata/genética , Linfócitos T CD4-Positivos/metabolismo , Regulação da Expressão Gênica , Humanos , Células Matadoras Naturais/metabolismo , Leucócitos/metabolismo , Masculino
3.
J Pathol ; 250(2): 205-216, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31639216

RESUMO

Diffuse malignant mesothelioma of the pleura (MPM) is a highly aggressive tumour that typically is associated with short survival. CD70 and CD27 belong to the tumour necrosis factor (TNF) and the TNF receptor (TNFR) superfamily, respectively. Under physiological conditions, the tightly regulated interaction between CD70 and CD27 plays a co-stimulatory role in promoting T-cell expansion and differentiation through the NFκB pathway. Aberrantly high CD70 expression has been documented in haematological and solid malignancies in association with immune evasion in malignant cells. In this study, 172 well-characterised primary diffuse MPM tumours including epithelioid (n = 145), biphasic (n = 15), and sarcomatoid (n = 12) histotypes were evaluated immunohistochemically for CD70, CD27, CD3, CD4, CD8, CD56, PDCD1 (PD-1), and FOXP3 expression. Twenty per cent (34/172) of the mesothelioma cells expressed CD70 on the cell membrane. Overall survival was significantly decreased in the cohort of patients with CD70-expressing tumour cells (p < 0.01). Patients with MPM containing a higher number of CD3+ (p < 0.01), CD4+ (p < 0.01), CD8+ (p < 0.01), or FOXP3+ (p < 0.01) tumour-infiltrating lymphoid cells (TILs) showed significantly worse clinical outcomes. As potential independent risk factors for MPM patients, multivariate Cox proportional hazards regression analysis revealed CD70 expression on mesothelioma cells [hazard ratio (HR) 2.25; p = 0.010], higher FOXP3+ TILs (HR 2.81; p = 0.004), and higher CD3+ TIL accumulation (HR 6.12; p < 0.001). In contrast, as a potential independent favourable factor, higher CD27+ TIL accumulation (HR 0.48; p = 0.037) was identified. In vitro experiments and an immunodeficient mouse model revealed that CD70 enhances the invasiveness of MPM cells through MET-ERK axis activation. Further analyses in syngeneic mouse models demonstrated possible roles for CD70 in immune evasion. Collectively, these findings suggest that the CD70-CD27 pathway enhances the malignant phenotypes of MPM and diminishes anti-tumor immune response in patients with these neoplasms. These markers might be useful in MPM for prognostic evaluations as well as targeted therapeutics. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Biomarcadores Tumorais/metabolismo , Ligante CD27/metabolismo , Neoplasias Pulmonares/imunologia , Mesotelioma/imunologia , Neoplasias Pleurais/imunologia , Evasão Tumoral/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antígenos CD/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Xenoenxertos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Linfócitos do Interstício Tumoral/imunologia , Mesotelioma/patologia , Mesotelioma Maligno , Camundongos Endogâmicos NOD , Pessoa de Meia-Idade , Invasividade Neoplásica , Transplante de Neoplasias , Neoplasias Pleurais/patologia , Prognóstico , Receptor de Morte Celular Programada 1/metabolismo
4.
Pol J Pathol ; 72(4): 358-369, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35308009

RESUMO

Primary cardiac sarcomas are extremely uncommon. We report two patients with primary cardiac atrial sarcomas: a case report of a 34-year old woman with intimal sarcoma of the left atrium and a case report of a 30-year old man with synovial sarcoma of the right atrium. Clinicopathological and differential diagnosis with a discussion regarding the role of molecular studies is presented.


Assuntos
Neoplasias Cardíacas , Sarcoma Sinovial , Sarcoma , Adulto , Diagnóstico Diferencial , Feminino , Átrios do Coração/patologia , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/patologia , Humanos , Masculino , Sarcoma Sinovial/genética
5.
Int J Mol Sci ; 22(11)2021 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-34071045

RESUMO

The association of immune markers and clinicopathologic features and patient outcome has not been extensively studied in Merkel cell carcinoma (MCC). We correlated tumoral PD-L1 and IDO1 expression, and intratumoral CD8+ and FoxP3+ lymphocytes count with clinicopathologic variables, Merkel cell polyomavirus (MCPyV) status, and patient outcomes in a series of 132 MCC. By univariate analyses, tumoral PD-L1 expression >1% and combined tumoral PD-L1 >1% and high intratumoral FoxP3+ lymphocyte count correlated with improved overall survival (OS) (p = 0.016, 0.0072), MCC-specific survival (MSS) (p = 0.019, 0.017), and progression-free survival (PFS) (p = 0.043, 0.004, respectively). High intratumoral CD8+ and FoxP3+ lymphocyte count correlated with longer MSS (p = 0.036) and improved PFS (p = 0.047), respectively. Ulceration correlated with worse OS and worse MSS. Age, male gender, and higher stage (3 and 4) significantly correlated with worse survival. MCPyV positivity correlated with immune response. By multivariate analyses, only ulceration and age remained as independent predictors of worse OS; gender and stage remained for shorter PFS. Tumoral PD-L1 expression and increased density of intratumoral CD8+ lymphocytes and FoxP+ lymphocytes may represent favorable prognosticators in a subset of MCCs. Tumoral PD-L1 expression correlated with intratumoral CD8+ and FoxP3+ lymphocytes, which is supportive of an adaptive immune response.


Assuntos
Antígeno B7-H1/biossíntese , Linfócitos T CD8-Positivos/imunologia , Carcinoma de Célula de Merkel/mortalidade , Indolamina-Pirrol 2,3,-Dioxigenase/biossíntese , Linfócitos do Interstício Tumoral/imunologia , Proteínas de Neoplasias/biossíntese , Neoplasias Cutâneas/mortalidade , Subpopulações de Linfócitos T/imunologia , Imunidade Adaptativa , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Linfócitos T CD8-Positivos/química , Carcinoma de Célula de Merkel/química , Carcinoma de Célula de Merkel/imunologia , Carcinoma de Célula de Merkel/virologia , Feminino , Fatores de Transcrição Forkhead/análise , Neoplasias de Cabeça e Pescoço/química , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Estimativa de Kaplan-Meier , Contagem de Linfócitos , Masculino , Poliomavírus das Células de Merkel/isolamento & purificação , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Segunda Neoplasia Primária/química , Segunda Neoplasia Primária/imunologia , Segunda Neoplasia Primária/mortalidade , Segunda Neoplasia Primária/virologia , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Fatores Sexuais , Neoplasias Cutâneas/química , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/virologia , Úlcera Cutânea/etiologia , Infecções Tumorais por Vírus
6.
Int J Cancer ; 146(5): 1293-1298, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31469414

RESUMO

Methylation of the promoter of the BRCA1 gene in DNA derived from peripheral blood cells is a possible risk factor for breast cancer. It is not clear if this association is restricted to certain types of breast cancer or is a general phenomenon. We evaluated BRCA1 methylation status in peripheral blood cells from 942 breast cancer patients and from 500 controls. We also assessed methylation status in 262 paraffin-embedded breast cancer tissues. Methylation status was assessed using methylation-sensitive high-resolution melting and was categorized as positive or negative. BRCA1 methylation in peripheral blood cells was strongly associated with the risk of triple-negative breast cancer (TNBC) (odds ratio [OR] 4.70; 95% confidence interval [CI]: 3.13-7.07; p < 0.001), but not of estrogen-receptor positive breast cancer (OR 0.80; 95% CI: 0.46-1.42; p = 0.46). Methylation was also overrepresented among patients with high-grade cancers (OR 4.53; 95% CI: 2.91-7.05; p < 0.001) and medullary cancers (OR 3.08; 95% CI: 1.38-6.88; p = 0.006). Moreover, we detected a significant concordance of BRCA1 promoter methylation in peripheral blood and paired tumor tissue (p < 0.001). We found that BRCA1 promoter methylation in peripheral blood cells is associated with approximately five times greater risk of TNBC. We propose that BRCA1 methylation in blood-derived DNA could be a novel biomarker of increased breast cancer susceptibility, in particular for triple-negative tumors.


Assuntos
Proteína BRCA1/genética , Biomarcadores Tumorais/genética , Predisposição Genética para Doença , Regiões Promotoras Genéticas/genética , Neoplasias de Mama Triplo Negativas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Mama/patologia , Estudos de Casos e Controles , Metilação de DNA , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Neoplasias de Mama Triplo Negativas/sangue , Neoplasias de Mama Triplo Negativas/patologia
7.
Am J Dermatopathol ; 42(9): 629-640, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32833736

RESUMO

Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine carcinoma of unknown origin. We performed a retrospective histologic review of primary cutaneous MCCs diagnosed from 1997 to 2018 in several clinical institutions and literature review to determine the frequency of various unusual morphologic appearances of MCC. Of the 136 primary MCCs identified, intraepidermal carcinoma or epidermotropism was noted in 11/136 (8%) cases. An association with pilar cyst in 1/136 (0.7%) case, with actinic keratosis in 2/136 (1.5%) cases, with either invasive or in situ squamous cell carcinoma (SCC) in 14/136 (10%) cases, with poroma in 1/136 (0.7%), and with basal cell carcinoma in 1/136 (0.7%) case was noted. Trabecular pattern and rosettes were noted in 7/136 (5%) and 3/136 (2%) cases, respectively. There was one case of metastatic MCC in a lymph node with chronic lymphocytic leukemia and one rare case of metastatic MCC and SCC in a lymph node. Although uncommon, differentiation toward other cell lineage can be observed in both primary and metastatic MCCs. The tumor can assume a variety of histologic appearances including association with SCC, basal cell carcinoma, melanocytic neoplasm, and follicular cyst; as well as exhibit glandular, sarcomatous, and mesenchymal differentiation. This diversity of morphologic appearance of MCC reflects the complexity of its underlying pathogenesis.


Assuntos
Carcinoma de Célula de Merkel/patologia , Células de Merkel/patologia , Neoplasias Cutâneas/patologia , Biomarcadores Tumorais/análise , Biópsia , Carcinoma de Célula de Merkel/química , Carcinoma de Célula de Merkel/imunologia , Diferenciação Celular , Diagnóstico Diferencial , Humanos , Hospedeiro Imunocomprometido , Imuno-Histoquímica , Metástase Linfática , Células de Merkel/química , Células de Merkel/imunologia , Polônia , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Neoplasias Cutâneas/química , Neoplasias Cutâneas/imunologia , Taiwan , Estados Unidos
8.
Pol J Pathol ; 71(1): 7-12, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32429649

RESUMO

Phyllodes tumor of the breast (PTB) is a rare neoplasm and accounts for 0.2-2.0% of breast cancer in women. Histopathological diagnosis of the tumor is difficult, and histological features do not always predict the course of the disease and the risk of progression. Pathogenesis and molecular biological characteristics as well as PTB prognostic factors are unknown. In search for genetic factors affecting PTB progression, 10 patients were analyzed for whom material from the primary tumor and local recurrence was available. DNA isolated from paraffin blocks was sequenced using the next-generation sequencing method (NGS). In 4 pairs, consisting of primary tumor and local recurrence, probably pathogenic/pathogenic variants were detected, and in three pairs they were observed in the CDKN2A gene, while other variants were found in PTEN and TP53 genes. NGS results indicate that the above-mentioned variants are hereditary, which suggests that the CDKN2A gene might be involved in cancerogenesis of PTB. Additionally, the selected pathogenic variant of EGFR gene was exclusively detected in one recuurent tumor, which might suggest the involvement of this gene in the mechanism of progression. In order to determine if this variant is associated with progression, the frequency of this mutation should be examined in larger group of malignant and borderline tumors.


Assuntos
Neoplasias da Mama/genética , Mutação , Tumor Filoide/genética , Feminino , Genes erbB-1 , Genes p16 , Genes p53 , Humanos , Recidiva Local de Neoplasia , PTEN Fosfo-Hidrolase
9.
Pol J Pathol ; 71(2): 181-193, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32729309

RESUMO

Synovial sarcoma is a rare mesenchymal malignant neoplasm that presents a specific t(X;18) translocation forming SS18(SYT)-SSX chimera gene. It is most commonly seen in soft tissues of the extremities. The digestive tract is an exceptional site of involvement. We report a case of primary gastric synovial sarcoma in a 48-year-old female. Differential diagnosis of synovial sarcoma from other spindle cell, mesenchymal and cytokeratin-positive tumors is critical for the treatment and prognosis. Immunohistochemistry studies and molecular analysis are required to settle a proper diagnosis.


Assuntos
Sarcoma Sinovial , Feminino , Humanos , Pessoa de Meia-Idade , Imuno-Histoquímica , Proteínas de Fusão Oncogênica/genética , Sarcoma Sinovial/genética , Translocação Genética
10.
Pol J Pathol ; 70(4): 277-285, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32146797

RESUMO

Currently there is being conducted an extensive search to find new prognostic factors in oral squamous cell carcinoma which would assist in better patient management. One of the most promising prognostic markers is the density of tumour infiltrating lymphocytes. 100 cases of patients with oral squamous cell carcinoma that underwent surgical resection between 2006 and June 2016 at our institution were included in this study. From each case the most representative HE stained slide was identified and the density of tumour infiltrating lymphocytes were classified as non-brisk or brisk, which was included in the survival analysis. Upon analysis there was a strong correlation between non-brisk (n = 28) and brisk (n = 72) tumour infiltrating lymphocytes and the primary clinical outcomes: overall survival (p = 0.0472) and local recurrence-free survival (p = 0.00037). Univariate and multivariate Cox regression model confirmed the high prognostic value of tumour infiltrating lymphocytes as the independent prognostic indicator of better survival, being even superior, in our study, to the traditional pTNM system. This study provides robust evidence that the density of tumour infiltrating lymphocytes demonstrates a high prognostic significance in oral squamous cell carcinoma.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Linfócitos do Interstício Tumoral/citologia , Neoplasias Bucais/diagnóstico , Carcinoma de Células Escamosas/imunologia , Humanos , Neoplasias Bucais/imunologia , Prognóstico
11.
Pol J Pathol ; 70(2): 148-152, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31556568

RESUMO

Fibrosarcomas are placed among the most infrequent malignant tumors of the uterus. We present a case of a 38 years-old woman, whose benign looking uterine mass was primary diagnosed as a sclerosing leiomyoma. However, the tumor relapsed in two years with multisite metastases in the abdomen. The complex differential diagnosis excluded the most common mesenchymal tumors of the gynecological tract. Finally, we diagnosed the tumor as an epithelioid sclerosing fibrosarcoma arising from the uterine.


Assuntos
Fibrossarcoma/diagnóstico , Leiomioma/diagnóstico , Útero/patologia , Adulto , Diagnóstico Diferencial , Feminino , Humanos
12.
Genome Res ; 25(10): 1521-35, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26430163

RESUMO

Sporadic breast cancer (SBC) is a common disease without robust means of early risk prediction in the population. We studied 282 females with SBC, focusing on copy number aberrations in cancer-free breast tissue (uninvolved margin, UM) outside the primary tumor (PT). In total, 1162 UMs (1-14 per breast) were studied. Comparative analysis between UM(s), PT(s), and blood/skin from the same patient as a control is the core of the study design. We identified 108 patients with at least one aberrant UM, representing 38.3% of cases. Gains in gene copy number were the principal type of mutations in microscopically normal breast cells, suggesting that oncogenic activation of genes via increased gene copy number is a predominant mechanism for initiation of SBC pathogenesis. The gain of ERBB2, with overexpression of HER2 protein, was the most common aberration in normal cells. Five additional growth factor receptor genes (EGFR, FGFR1, IGF1R, LIFR, and NGFR) also showed recurrent gains, and these were occasionally present in combination with the gain of ERBB2. All the aberrations found in the normal breast cells were previously described in cancer literature, suggesting their causative, driving role in pathogenesis of SBC. We demonstrate that analysis of normal cells from cancer patients leads to identification of signatures that may increase risk of SBC and our results could influence the choice of surgical intervention to remove all predisposing cells. Early detection of copy number gains suggesting a predisposition toward cancer development, long before detectable tumors are formed, is a key to the anticipated shift into a preventive paradigm of personalized medicine for breast cancer.


Assuntos
Neoplasias da Mama/genética , Mama/anatomia & histologia , Mutação , Adulto , Idoso , Idoso de 80 Anos ou mais , Mama/patologia , Neoplasias da Mama/patologia , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Dosagem de Genes , Genes erbB-2 , Predisposição Genética para Doença , Genótipo , Humanos , Pessoa de Meia-Idade , Receptor ErbB-2/genética , Receptores de Fatores de Crescimento/genética , Fatores de Risco
13.
Pol J Pathol ; 69(3): 285-291, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30509055

RESUMO

Within the past years the proportion of cervical adenocarcinomas has increased, however, there is a shortage of data regarding immunohistochemical and molecular features and their prognostic relevance in early-stage cervical adenocarcinoma (esCAC). Aim of the present study was to evaluate molecular prognostic factors in esCAC patients treated with primary surgery. Analyses of surgical specimens in 59 patients with esCAC were performed on fixed paraffin-embedded sections of tumour tissue. Tumour tissue sections were routinely stained with hematoxylin and eosin followed by microscopic examination. Immunohistochemical analyses (IHC) were performed on paraffin-embedded section. Flow cytometry (FCM) analysis of paraffin-embedded tumor tissue was performed using flow cytometer FACSCalibur equipped with argon laser. DNA histogram analysis was performed with ModFit application. Treatment effectiveness was evaluated using overall 5-year survival. Survival probability was estimated using the Kaplan-Meier method. Overall survival rate estimated using Kaplan-Meier method was 74.6%. Among the IHC and FCM features univariate analysis showed statistical significance of nm23-H1 gene expression and total S-phase fraction ≤ 11.9% (S-TOT). In multi- variate analysis LVSI and parametrial involvement had significant, negative impact on survival (HR = 8.04, p < 0.003 and HR = 4.03, p < 0.017, respectively). However, none of the tested IHC and FCM features had any influence on overall 5-year survival.


Assuntos
Adenocarcinoma/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Feminino , Citometria de Fluxo , Humanos , Estadiamento de Neoplasias , Prognóstico
14.
Dev Period Med ; 22(4): 358-363, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30636233

RESUMO

The aim of this paper is a clinical and anatomopathological demonstration of a malignant lesion, a gastrointestinal neuroectodermal tumor (GNET), as an exceedingly rare cause of ileus in the pediatric population. Specifically, we present the case of a 12-year-old boy who showed dramatic weight loss, hypochromic anemia, fever, dehydration, exaggerated granulation of the terminal ileum, and mechanical ileus due to the obstruction by an intramural tumor of the small intestine. A 50cm-long part of the small intestine with pathological stricture was surgically removed, sampled and routinely fixed and stained with hematoxylin and eosin. The additional immunostains that were preformed were: PAS, S-100, HMB-45, NSE, LCA, CK AE1 / AE3, desmin, SMA, vimentin, CD99, NSE, synaptophysin, WT-1, calretinin, and DOG-1. Moreover, fluorescent in situ hybridization (FISH) with the EWSR1 Break Apart FISH Probe was applied. The neoplasm was composed of nests and alveolar patterns of frankly malignant clear cells with immunoreactivity to S-100, vimentin, and CD 99. The FISH technique detected chromosomal breaking at 22q12. The tumor metastasized to both the mesenteric lymph nodes and a number of hepatic segments. With several chemotherapy protocols, repeat laparotomies, and liver thermal ablations, the patient had a 1.5-year-long survival from the moment of diagnosis. The diagnosis of this malignancy requires both histopathological evaluation and molecular analysis, and the follow-up is based on careful clinical imaging of the neoplastic spread in order to apply proper surgical and oncological treatments. In conclusion, the clinical course of GNET was highly aggressive.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/tratamento farmacológico , Tumores Neuroectodérmicos/diagnóstico , Tumores Neuroectodérmicos/tratamento farmacológico , Sarcoma de Células Claras/diagnóstico , Sarcoma de Células Claras/tratamento farmacológico , Biópsia , Criança , Técnicas de Ablação Endometrial , Neoplasias Gastrointestinais/cirurgia , Humanos , Hibridização in Situ Fluorescente , Masculino , Tumores Neuroectodérmicos/cirurgia , Polônia , Doenças Raras/diagnóstico , Doenças Raras/tratamento farmacológico , Doenças Raras/cirurgia , Sarcoma de Células Claras/cirurgia , Resultado do Tratamento
15.
Angiogenesis ; 20(3): 325-340, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28197812

RESUMO

Monocyte Chemoattractant protein-induced protein 1 (MCPIP1), also known as Regnase-1, is encoded by the ZC3H12a gene, and it mediates inflammatory processes by regulating the stability of transcripts coding for proinflammatory cytokines and controlling activity of transcription factors, such as NF-κB and AP1. We found that MCPIP1 transcript and protein levels are strongly downregulated in clear cell renal cell carcinoma (ccRCC) samples, which were derived from patients surgically treated for renal cancer compared to surrounded normal tissues. Using Caki-1 cells as a model, we analyzed the role of MCPIP1 in cancer development. We showed that MCPIP1 expression depends on the proteasome activity; however, hypoxia and hypoxia inducible factor 2 alfa (HIF2α) are key factors lowering MCPIP1 expression. Furthermore, we found that MCPIP1 negatively regulates HIF1α and HIF2α levels and in the case of the last one, the mechanism is based on the regulation of the half time of transcript coding for HIF2α. Enhanced expression of MCPIP1 in Caki-1 cells results in a downregulation of transcripts encoding VEGFA, GLUT1, and IL-6. Furthermore, MCPIP1 decreases the activity of mTOR and protein kinase B (Akt) in normoxic conditions. Taken together, MCPIP1 contributes to the ccRCC development.


Assuntos
Carcinogênese/metabolismo , Carcinogênese/patologia , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Ribonucleases/metabolismo , Fatores de Transcrição/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Hipóxia Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Transportador de Glucose Tipo 1/metabolismo , Humanos , Leupeptinas/farmacologia , Masculino , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Inibidores de Proteassoma/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ribonucleases/genética , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
16.
Pol J Pathol ; 68(4): 343-351, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29517205

RESUMO

Department of Tumour Pathology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Kraków, Poland The review of literature indicates that several clinico-morphological factors such as location of the primary tumour as well as its size, histologic subtype, and grade or even selected molecular changes may significantly affect survival of liposarcoma (LPS) patients. Data concerning prognostic importance of DNA ploidy status in LPS cells are extremely limited and results of flow cytometry (FCM) studies have never been compiled with the current classification of malignant adipocytic tumours. Based on evaluation of material from 54 liposarcomas which was available for both histological and FCM analysis, we distinguished four prognostic groups of patients. The best prognosis was noticed for diploid and grade G1 well-differentiated or myxoid liposarcomas localised on extremities. None of the patients with lipoma-like WDLPS and myxoid liposarcoma grade 1 metastasised, while metastases were observed among patients with dedifferentiated LPS (70% of 5-year MFS) and cellular myxoid or round cell liposarcoma (20% of 5-year MFS, only). The metastasis-free survival curves for the above mentioned groups of patients differed significantly (p = 0.00001).


Assuntos
Diferenciação Celular , Lipossarcoma Mixoide/genética , Lipossarcoma Mixoide/patologia , Lipossarcoma/genética , Lipossarcoma/patologia , Ploidias , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Lipossarcoma/mortalidade , Lipossarcoma/terapia , Lipossarcoma Mixoide/mortalidade , Lipossarcoma Mixoide/terapia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
18.
Med Sci Monit ; 22: 3886-3893, 2016 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-27768681

RESUMO

BACKGROUND Contrast enhanced spectral mammography (CESM) is a new method of breast cancer diagnosis in which an iodinated contrast agent is injected and dual-energy mammography is obtained in multiple views of the breasts. The aim of this study was to compare the degree of enhancement on CESM with lesion characteristics on mammography (MG) and lesion histology in women with suspicious breast lesions. MATERIAL AND METHODS The degree of enhancement on CESM (absent, weak, medium, or strong) was compared to lesion characteristics on MG (mass, mass with microcalcifications, or microcalcifications alone) and histology (infiltrating carcinoma, intraductal carcinoma, or benign) to compare sensitivity of the two modalities and to establish correlations that might improve diagnostic accuracy. RESULTS Among 225 lesions identified with CESM and MG, histological evaluation revealed 143 carcinomas (127 infiltrating, 16 intraductal) and 82 benign lesions. This is the largest cohort investigated with CESM to date. The sensitivity of CESM was higher than that of MG (100% and 90%, respectively, p=0.010). Medium or strong enhancement on CESM and the presence of a mass on MG was the most likely indictor of malignancy (55.1% p=0.002). Among benign lesions, 60% presented as enhancement on CESM (were false-positive), and most frequently as medium or weak enhancement, together with a mass on MG (53%, p=0.047). Unfortunately, the study did not find combinations of MG findings and CESM enhancement patterns that would be helpful in defining false-positive lesions. We observed systematic overestimation of maximum lesion diameter on CESM compared to histology (mean difference: 2.29 mm). CONCLUSIONS Strong or medium enhancement on CESM and mass or mass with microcalcifications on MG were strong indicators of malignant transformation. However, we found no combination of MG and CESM characteristics helpful in defining false-positive lesions.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Mamografia/métodos , Mama/diagnóstico por imagem , Mama/patologia , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Meios de Contraste , Feminino , Humanos , Pessoa de Meia-Idade
19.
Med Sci Monit ; 22: 2691-8, 2016 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-27474270

RESUMO

BACKGROUND Radiotherapy is explicitly indicated as one of the excluding factors in diagnosing overactive bladder syndrome (OAB). Nevertheless, symptoms of OAB such as urgent episodes, incontinence, pollakiuria, and nocturia, which are consequences of irradiation, led us to test the effectiveness of VESIcare®/Solifenacin in patients demonstrating these symptoms after radiation therapy of small pelvis organs due to malignant neoplasm. MATERIAL AND METHODS We conducted an observatory clinical study including 300 consecutive patients with symptoms of post-irradiation bladder; 271 of those patients completed the study. The observation time was 6 months and consisted of 3 consecutive visits taking place at 12-week intervals. We used VESIcare® at a dose of 5 mg a day. Every sixth patient was examined urodynamically at the beginning and at the end of the observation period, with an inflow speed of 50 ml/s. RESULTS We noticed improvement and decline in the average number of episodes a day in the following parameters: number of micturitions a day (-36%, P<0.01), nocturia (-50%, P<0.01), urgent episodes (-41%, P<0.03), and episodes of incontinence (-43%, P<0.01). The patients' quality of life improved. The average maximal cystometric volume increased by 34 ml (21%, p<0.01), average bladder volume of "first desire" increased by 42 ml (49%, P<0.01), and average detrusor muscle pressure at maximal cystometric volume diminished by 9 cmH2O (-36%, P<0.03). CONCLUSIONS The substance is well-tolerated. Solifenacin administered long-term to patients with symptoms of OAB after radiotherapy of a malignant neoplasm of the small pelvis organs has a daily impact in decreasing number of urgent episodes, incontinence, pollakiuria, and nocturia.


Assuntos
Neoplasias Pélvicas/radioterapia , Lesões por Radiação/tratamento farmacológico , Lesões por Radiação/etiologia , Succinato de Solifenacina/uso terapêutico , Doenças da Bexiga Urinária/tratamento farmacológico , Doenças da Bexiga Urinária/etiologia , Bexiga Urinária/efeitos da radiação , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pelve/efeitos da radiação , Qualidade de Vida , Síndrome , Resultado do Tratamento
20.
Pol J Pathol ; 67(4): 398-403, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28547969

RESUMO

The aim of the study was to assess the relationship between the apparent diffusion coefficient in diffusion-weighted magnetic (DWM) resonance imaging (MRI) and selected morphological parameters of the breast lesions. Diffusion-weighted imaging data and the pathology reports of 160 women treated surgically between January 2011 and March 2015 were analyzed. When classified, 107 invasive carcinomas, 13 pre-invasive carcinomas and 40 benign lesions were identified. The mean apparent diffusion coefficient was significantly lower for invasive carcinomas than benign lesions of the breast (0.87 ±0.02 vs. 1.58 ±0.04; p < 0.001). What is more there was an inverse correlation between value of apparent diffusion coefficient in diffusion-weighted magnetic resonance imaging and the grade of breast carcinomas (p = 0.04).


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem
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