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Several cytokines and chemokines are involved in the pathogenesis and progressive injury of renal tissues in patients with primary chronic glomerulonephritis (CGN). The objective of this study was to determine whether the urinary excretion of interleukin-6 (IL-6), transforming growth factor ß1 (TGFß1), monocytes chemoattractant protein (MCP-1), soluble tumor necrosis factor receptor 1 (sTNFR1), and epidermal growth factor (EGF) in patients with newly recognized CGN can serve as prognostic biomarkers in patients with newly recognized CGN and whether they can be effective in predicting a progressive reduction of renal function in prospective observation. The study included 150 Caucasian patients. UIL-6, UTGFß1, UMCP-1, UsTNFR1, and UEGF were measured using enzyme-linked immunosorbent assay (ELISA) methods (Quantikine R&D System). UIL-6, UTGFß1, UMCP-1, and UsTNFR1 were significantly higher, yet UEGF excretion was significantly lower in nephrotic patients, in patients with estimated glomerular filtration rate (eGFR) < 60/min/1.73 m2 at presentation, as well as in the progressor (PG) subgroup. In a multivariate regression analysis basal eGFR correlated with UsTNFR1, UIL-6, and UEGF excretion, although in the follow-up, ΔeGFR (delta estimated glomerular filtration rate) significantly correlated only with UEGF excretion. A logistic regression analysis showed that the most significant independent risk factors for the deterioration of renal function with time are initial high (>11.8 pg/mgCr) UIL-6 excretion, initial low (<15.5 ng/mgCr) urinary UEGF excretion, and male gender. In patients with newly diagnosed CGN, UIL-6, and UEGF can serve as prognostic biomarkers for the progression of the disease.NEW & NOTEWORTHY Baseline high urinary interleukin-6 (IL-6) excretion and low urinary epidermal growth factor (EGF) excretion and particularly high IL-6/EGF ratio were stronger predictive factors of the progression of the deterioration of the kidney function than initial estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or proteinuria. In patients with newly diagnosed chronic glomerulonephritis, UIL-6 and UEGF can serve as prognostic biomarkers for the progression of the disease.
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Fator de Crescimento Epidérmico , Glomerulonefrite , Humanos , Masculino , Fator de Crescimento Epidérmico/urina , Interleucina-6 , Estudos Prospectivos , Progressão da Doença , Doença Crônica , Glomerulonefrite/diagnóstico , Biomarcadores/urinaRESUMO
Despite the progress made in treating bipolar and unipolar affective disorders, lithium carbonate is still a common drug in psychiatric practice. Lithium-related renal side effects include nephrogenic diabetes insipidus, chronic tubulointerstitial nephropathy, and acute kidney injury (AKI). Nephrotic syndrome (NS) is an uncommon but severe complication of lithium treatment. We present a 49-year-old female treated with lithium carbonate due to a recurrent depressive disorder who developed NS during this therapy. NS spontaneously remitted after the drug withdrawal. Since her lithium serum levels were within the recommended values, we performed a retrospective analysis of lithium-induced NS cases trying to determine causes predisposing to the NS development, underlying histopathology, and preservation or irreversible loss of kidney function. This analysis revealed that in lithium-induced NS with AKI, lithium serum level was the key determinant of AKI development (the ß coefficient = 0.8499 with a confidence interval ranging from 0.7452 to 0.9546 and p value < 0.0001). In these cases, the underlying pathology was mainly minimal change disease (MCD), which was quickly reversible upon the drug withdrawal. The development of chronic kidney disease (CKD) seemed to be associated with lithium therapy duration. However, the multiple regression analysis for CKD as the dependent variable showed that the decisive factor was focal segmental glomerulosclerosis (FSGS) as the underlying pathology (the ß coefficient = 0.7866 with a confidence interval ranging from 0.600 to 0.9704 and the p value < 0.0001). Thus, we conclude that in lithium-induced NS/AKI, serum lithium levels contribute to these complications, while FSGS lesions are responsible for CKD's disease progression.
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Injúria Renal Aguda/fisiopatologia , Compostos de Lítio/toxicidade , Lítio/toxicidade , Nefrose Lipoide/fisiopatologia , Síndrome Nefrótica/fisiopatologia , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/patologia , Progressão da Doença , Rim/efeitos dos fármacos , Rim/patologia , Rim/fisiopatologia , Nefrose Lipoide/induzido quimicamente , Nefrose Lipoide/patologia , Síndrome Nefrótica/induzido quimicamente , Síndrome Nefrótica/patologiaRESUMO
Immunologically different types of glomerulopathies show varied symptoms and clinical courses. Unlike in lupus nephritis, repeated biopsy is rarely performed in cases of mesangial glomerulonephritis. We reviewed 200 cases wherein rebiopsy was performed in patients with diagnosed mesangial glomerular pathology over a 30-year period and analyzed the symptoms follow-up in these cases. Further, we evaluated the morphological changes between the first and final biopsies to identify cases of histological progression and histological remission and examined the correlation between such changes and clinical symptoms. The time between the first and last biopsies ranged from 7 months to 35 years. The most common for the initial biopsy was nephrotic syndrome, followed by non-nephrotic proteinuria; other symptoms occurred rarely. Histological progression occurred at various stages of observation, ranging from within a few months to after several years. Histological progression and remission were detected in 118 and 3 patients, respectively, whereas there was no difference in morphological findings between the first and last biopsies in 79 patients. Rebiopsy is useful in patients who do not respond adequately to treatment, and especially in those with increased clinical symptoms. Moreover, electron microscopic examination is necessary to discover early signs of histological progression.
Assuntos
Glomerulonefrite , Nefrite Lúpica , Biópsia , Glomerulonefrite/patologia , Humanos , Glomérulos Renais/patologia , Nefrite Lúpica/patologia , Microscopia EletrônicaRESUMO
We analyzed three cases of Complete Androgen Insensitivity Syndrome (CAIS) and report three hitherto undisclosed causes of the disease. RNA-Seq, Real-timePCR, Western immunoblotting, and immunohistochemistry were performed with the aim of characterizing the disease-causing variants. In case No.1, we have identified a novel androgen receptor (AR) mutation (c.840delT) within the first exon in the N-terminal transactivation domain. This thymine deletion resulted in a frameshift and thus introduced a premature stop codon at amino acid 282. In case No.2, we observed a nonsynonymous mutation in the ligand-binding domain (c.2491C>T). Case No.3 did not reveal AR mutation; however, we have found a heterozygous mutation in CYP11A1 gene, which has a role in steroid hormone biosynthesis. Comparative RNA-Seq analysis of CAIS and control revealed 4293 significantly deregulated genes. In patients with CAIS, we observed a significant increase in the expression levels of PLCXD3, TM4SF18, CFI, GPX8, and SFRP4, and a significant decrease in the expression of SPATA16, TSACC, TCP10L, and DPY19L2 genes (more than 10-fold, p < 0.05). Our findings will be helpful in molecular diagnostics of patients with CAIS, as well as the identified genes could be also potential biomarkers for the germ cells differentiation process.
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Síndrome de Resistência a Andrógenos/genética , Enzima de Clivagem da Cadeia Lateral do Colesterol/genética , Mutação , Receptores Androgênicos/genética , Análise de Sequência de DNA/métodos , Adolescente , Adulto , Síndrome de Resistência a Andrógenos/metabolismo , Estudos de Casos e Controles , Enzima de Clivagem da Cadeia Lateral do Colesterol/metabolismo , Éxons , Feminino , Mutação da Fase de Leitura , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Domínios Proteicos , Receptores Androgênicos/química , Receptores Androgênicos/metabolismo , Adulto JovemRESUMO
Coeliac disease (CD) is an autoimmune disorder of the small intestine triggered by ingested gluten from barley, rye and wheat. It can be associated with other autoimmune conditions, such as type 1 diabetes, autoimmune thyroiditis and hepatitis, Sjögren's syndrome and IgA nephropathy (IgAN). We describe here a case of a 24-year-old man with the above-mentioned atypical form of coeliac disease for whom the diagnosis started with renal disorder. The diagnosis of nephrotic syndrome was established and the coexistence with CD was also suspected. In fact, immunoglobulin (Ig) A and IgG antibodies against endomysium and against gliadin were detected in serum of the patient and the endoscopic biopsy of the duodenum revealed stage 3B CD. Percutaneous kidney biopsy was also performed. Class I IgAN was diagnosed. Gluten-free diet, ACE inhibitor and oral iron were introduced to the patient. The improvement of clinical and laboratory disorders of CD as well as gradual remission of the nephrotic syndrome were observed. In conclusion, there may be a small group of patients with IgAN coexisting with CD in whom a gluten-free diet seems to be the treatment of choice for the resolution of kidney disease.
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BACKGROUND: This is the first report on the epidemiology of biopsy-proven kidney diseases in Poland. METHODS: The Polish Registry of Renal Biopsies has collected information on all (n = 9394) native renal biopsies performed in Poland from 2009 to 2014. Patients' clinical data collected at the time of biopsy, and histopathological diagnoses were used for epidemiological and clinicopathologic analysis. RESULTS: There was a gradual increase in the number of native renal biopsies performed per million people (PMP) per year in Poland in 2009-14, starting from 36 PMP in 2009 to 44 PMP in 2014. A considerable variability between provinces in the mean number of biopsies performed in the period covered was found, ranging from 5 to 77 PMP/year. The most common renal biopsy diagnoses in adults were immunoglobulin A nephropathy (IgAN) (20%), focal segmental glomerulosclerosis (FSGS) (15%) and membranous glomerulonephritis (MGN) (11%), whereas in children, minimal change disease (22%), IgAN (20%) and FSGS (10%) were dominant. Due to insufficient data on the paediatric population, the clinicopathologic analysis was limited to patients ≥18 years of age. At the time of renal biopsy, the majority of adult patients presented nephrotic-range proteinuria (45.2%), followed by urinary abnormalities (38.3%), nephritic syndrome (13.8%) and isolated haematuria (1.7%). Among nephrotic patients, primary glomerulopathies dominated (67.6% in those 18-64 years of age and 62.4% in elderly patients) with leading diagnoses being MGN (17.1%), FSGS (16.2%) and IgAN (13.0%) in the younger cohort and MGN (23.5%), amyloidosis (18.8%) and FSGS (16.8%) in the elderly cohort. Among nephritic patients 18-64 years of age, the majority (55.9%) suffered from primary glomerulopathies, with a predominance of IgAN (31.3%), FSGS (12.7%) and crescentic GN (CGN) (11.1%). Among elderly nephritic patients, primary and secondary glomerulopathies were equally common (41.9% each) and pauci-immune GN (24.7%), CGN (20.4%) and IgAN (14.0%) were predominant. In both adult cohorts, urinary abnormalities were mostly related to primary glomerulopathies (66.8% in younger and 50% in elderly patients) and the leading diagnoses were IgAN (31.4%), FSGS (15.9%), lupus nephritis (10.7%) and FSGS (19.2%), MGN (15.1%) and pauci-immune GN (12.3%), respectively. There were significant differences in clinical characteristics and renal biopsy findings between male and female adult patients. CONCLUSIONS: The registry data focused new light on the epidemiology of kidney diseases in Poland. These data should be used in future follow-up and prospective studies.
Assuntos
Nefropatias/patologia , Rim/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Nefropatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Polônia/epidemiologia , Estudos Prospectivos , Sistema de Registros , Distribuição por Sexo , Adulto JovemRESUMO
The blood count test results of six patients (five male adolescents and one female adult) who were diagnosed with the hemolytic-uremic syndrome are presented. Certain diverse lesions and especially, their different intensity, were observed. They were referred to the clinical process and the time from syndrome occurrence to biopsy.
Assuntos
Injúria Renal Aguda/patologia , Membrana Basal Glomerular/ultraestrutura , Síndrome Hemolítico-Urêmica/patologia , Injúria Renal Aguda/diagnóstico , Adulto , Biópsia/métodos , Criança , Feminino , Síndrome Hemolítico-Urêmica/diagnóstico , Humanos , Lactente , Masculino , Microscopia/métodos , Microscopia Eletrônica/métodosRESUMO
Tumor-to-tumor metastases are very rare events. We report a case of a 64-year-old man who presented with a tumor of the pancreas. The patient underwent partial pancreatectomy. Frozen section diagnosis of the tumor was an endocrine neoplasm. Paraffin block slide examination revealed a tumor consisting of two components: pancreatic endocrine neoplasm at the periphery of the tumor and the central part composed of clear cells with delicate vessels. The results of immunohistochemical stains revealed renal cell carcinoma surrounded by pancreatic endocrine neoplasm, therefore representing an unusual case of renal cell carcinoma metastasizing to a pancreatic endocrine neoplasm.
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Carcinoma Neuroendócrino/patologia , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Neoplasias Primárias Múltiplas/patologia , Neoplasias Pancreáticas/patologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Nestin is considered to be a cancer stem cell marker. Nestin expression in neuroendocrine tumours might be useful to predict prognosis and facilitate treatment planning. 88 patients with neuroendocrine lung tumours operated in the Department of Thoracic Surgery from 2007 to 2015 were included into the study. Immunohistochemical staining for nestin was performed. Clinicopathological and survival data were retrospectively analyzed. Nestin expression was detected in 15 (17%) specimens. Multivariate analysis showed that lymph node metastases (p = 0.0001; hazard ratio (HR) = 3.93; confidence interval (CI) 95%: 1.96-7.87), nestin expression (p = 0.034; HR = 2.30; CI 95%: 1.06-4.99) and patient's age (p = 0.024; HR = 1.04; CI 95%: 1.00-1.09) were independent negative prognostic factors. Nestin expression was significantly higher in large cell neuroendocrine carcinoma when compared with carcinoids (p = 0.001). Collected data support the thesis that nestin can be regarded as a biomarker in patients with neuroendocrine lung tumours.
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Biomarcadores Tumorais/análise , Tumor Carcinoide/química , Neoplasias Pulmonares/química , Nestina/análise , Tumores Neuroendócrinos/química , Adulto , Fatores Etários , Idoso , Tumor Carcinoide/mortalidade , Tumor Carcinoide/secundário , Tumor Carcinoide/cirurgia , Distribuição de Qui-Quadrado , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/secundário , Tumores Neuroendócrinos/cirurgia , Pneumonectomia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
We examined a group of 83 patients (57 children and 26 adults) with thin basement membrane disease and 17 patients with Alport syndrome. We compared the clinical data and, above all, the morphological patterns of both disease entities, with particular focus on not very advanced changes which might lead to a misdiagnosis due to the non-detection of the early stages of Alport syndrome.
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Membrana Basal/patologia , Nefropatias/diagnóstico , Nefrite Hereditária/diagnóstico , Adolescente , Adulto , Idoso , Membrana Basal/ultraestrutura , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Imunofluorescência , Humanos , Nefropatias/patologia , Masculino , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , Adulto JovemRESUMO
The aim of this study was to assess the epidemiology of different patterns of chronic glomerular diseases based on clinical, histopathological and immunofluorescent findings of glomerulonephritis patients hospitalized in the Department of Nephrology, Transplantology and Internal Diseases in Poznan between January 2009 and December 2012. We retrospectively studied 418 patients who had been subjected to renal biopsies. Data on serum creatinine concentration, 24 h proteinuria, arterial hypertension, diabetes mellitus, and histological and immunofluorescent findings were collected. The patients' mean age was 42 ±15. The male sex prevailed (53.1%). Immunoglobulin A nephropathy was the most common finding (18.9%), followed by focal segmental glomerulosclerosis (16.3%), membranous glomerulonephritis (10.1%), lupus nephritis (8.4%), extracapillary glomerulonephritis (3.3%) and membranoproliferative glomerulonephritis (2.6%). In 69 (16.5%) patients the biopsy was non-informative or non-diagnostic. Patients with membranous nephropathy presented the highest frequency of nephrotic syndrome (71.4%), followed by membranoproliferative glomerulonephritis and focal segmental glomerulosclerosis. Combined analysis of the clinical, histopathological and immunofluorescent findings in glomerulonephritis patients based on a single center's data can provide important epidemiological findings.
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Nefropatias/patologia , Glomérulos Renais/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Imunofluorescência , Humanos , Nefropatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Polônia/epidemiologia , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: The main purpose of this study was the exact comparison of B-scan images obtained from 16 patients suffering from AD with histological. METHODS: Sixteen patients diagnosed with AD aged between 14 and 57 years, were chosen for the study. In all patients before the introduction of proper treatment regimen, the high frequency skin ultrasonography (Derma Scan Cortex Technology, version 3, Hadsund, Germany) has been performed and then a 5 mm wide punch biopsies have been taken from the area of scanned lesions. Control group consisted of 15 healthy individuals without any signs of atopic and chronic diseases. RESULTS: There was 7.8 ± 0.4% mean skin echogenicity from lesional antecubital skin in AD patients (min value 7.2%, max value 8.5%). The skin hypoechoic band was detected in fifteen out of sixteen patients (93.7%). There were statistically significant correlations between the hypoechoic band thickness and the following parameters: degree of epidermal hyperplasia, the degree of epidermal hyperkeratosis, the degree of parakeratosis and the degree of spongiosis as well as the intensity of inflammatory infiltrates. Skin echogenicity strongly correlated negatively with the intensity of inflammatory infiltrates. CONCLUSION: On the basis of analysis of 16 specimens we can conclude that all pathological changes of AD influence ultrasound image and in addition, the USG picture depends on the phase of disease process.
Assuntos
Dermatite Atópica/diagnóstico por imagem , Epiderme/diagnóstico por imagem , Índice de Gravidade de Doença , Ultrassonografia/métodos , Adolescente , Adulto , Biópsia , Dermatite Atópica/patologia , Epiderme/patologia , Feminino , Humanos , Hiperplasia/diagnóstico por imagem , Hiperplasia/patologia , Ceratose/diagnóstico por imagem , Ceratose/patologia , Masculino , Pessoa de Meia-Idade , Paraceratose/diagnóstico por imagem , Paraceratose/patologia , Ultrassonografia/instrumentação , Adulto JovemRESUMO
Henoch-Schoenlein nephritis (HSN) is the most common secondary childhood nephropathy, leading to end-stage renal disease in up to 20% of pediatric patients after long-term follow-up. Forty-four cases of HSN were reviewed (32 children, 12 adults). Electron microscopy (EM) was performed in 7 cases and immunohistochemistry for Ki-67, PCNA, and p27 in all. Light microscopy: grade II (18), III (15), IV (3), and VI (8). Glomerulosclerosis and interstitial fibrosis were important prognostic markers and coexisted with poor outcome. EM was performed mainly in grade VI and was useful in recognition of early glomerulosclerosis. No correlations were found between the Ki67 and PCNA mesangial expression and outcome. Progressive decrease in p27 podocyte expression was noted with more severe HSN grades.
Assuntos
Glomerulonefrite/diagnóstico , Vasculite por IgA/diagnóstico , Imuno-Histoquímica , Rim/química , Rim/ultraestrutura , Microscopia Eletrônica , Adolescente , Adulto , Biomarcadores/análise , Biópsia , Criança , Pré-Escolar , Inibidor de Quinase Dependente de Ciclina p27/análise , Feminino , Fibrose , Glomerulonefrite/metabolismo , Glomerulonefrite/patologia , Humanos , Vasculite por IgA/metabolismo , Vasculite por IgA/patologia , Antígeno Ki-67/análise , Masculino , Pessoa de Meia-Idade , Podócitos/química , Podócitos/ultraestrutura , Prognóstico , Antígeno Nuclear de Célula em Proliferação/análise , Índice de Gravidade de Doença , Adulto JovemRESUMO
BACKGROUND: Tumor necrosis factor receptor 1 (TNFR1) and 2 (TNFR2) can be cleaved from the cell surface and circulate alone or in combination with tumor necrosis factor alpha (TNF-α). These soluble receptors may play a key role in regulating the inflammatory response. OBJECTIVES: The study aimed to evaluate the role of TNFRs in regulating the inflammatory response in immunoglobulin A nephropathy (IgAN). MATERIAL AND METHODS: The study included 26 patients with newly diagnosed and biopsy-confirmed IgAN and 20 healthy controls. Study material included blood and fresh urine collected the morning before kidney biopsy and therapy. The serum concentrations of TNFR1 (STNFR1) and TNFR2 (STNFR2) and urinary excretion of TNFR1 (UTNFR1) and TNFR2 (UTNFR2) were determined with immunoassay. Subsequently, the data were evaluated statistically. RESULTS: The STNFR1 and STNFR2 levels were higher in IgAN patients than in healthy subjects (4747.87 pg/mL and 2817.62 pg/mL compared to 2755.68 pg/mL (95% CI: from -2948.41 to -1035.97; p = 0.001) and 1437.83 pg/mL (95% CI: from -1958.50 to -419.60; p = 0.001). The power of the test was 98.5% for STNFR1 and 96% for STNFR2. Urinary concentrations only increased for TNFR1 (3551.29 compared to 2338.95 pg/mg of creatinine (Cr) (95% CI: from -2247.03 to -177.66; p = 0.023). The STNFR1 marker was characterized by a sensitivity of 73.08% and a specificity of 90.00% (p < 0.001). CONCLUSIONS: Our results suggest that TNFR1 and TNFR2 are good markers of TNF-α pathway activation in IgAN patients.
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Focal segmental glomerulosclerosis (FSGS) is an important clinical problem as it leads to end-stage renal disease. Clinicians have long been able to treat patients with FSGS. Therefore, the demands the clinicians make on pathomorphologists, which include the diagnosis of FSGS at a possibly early stage, are justifiable. However, early diagnosis of FSGS is difficult. The analysis involved 150 cases of FSGS diagnosed between 2003 and 2008. These constitute 14.53% of renal biopsy material of that period. The test material comes from 138 adults and 12 children. The adult group mostly included patients with albuminuria (58 patients) and nephrotic syndrome (36 patients). Smaller groups included patients with albuminuria and hypertension, erythrocyturia and albuminuria, isolated erythrocyturia. The children group mostly included patients with the nephrotic syndrome. Individual patients suffered from isolated albuminuria and erythrocyturia. In both groups, FSGS NOS lesions prevailed. However, FSGS hilar and FSGS tip lesions, as well as completely sclerotized glomeruli were also present. Diverse symptoms of diseases may pose specific difficulties in clinical diagnosis. Similarly, determination of FSGS lesion type may be difficult due to simultaneous presence of different subtypes in the same punctate.
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Glomerulosclerose Segmentar e Focal/diagnóstico , Adolescente , Adulto , Idoso , Criança , Diagnóstico Precoce , Feminino , Imunofluorescência , Humanos , Masculino , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , Adulto JovemRESUMO
AIMS: The aim of the study is to correlate p16Ink4a expression with the clinical courses of pleomorphic adenoma (PA), its malignant transformation (CaexPA) and treatment outcomes. METHODS: Retrospective analysis (1998-2019) of 47 CaexPA, 148 PA and 22 normal salivary gland samples was performed. PAs were divided into two subsets: clinically 'slow' tumours characterised by stable size or slow growth; and 'fast' tumours with rapid growth rate. RESULTS: Positive p16Ink4a expression was found in 68 PA and 23 CaexPA, and borderline expression in 80 and 20, respectively. All 22 (100%) normal salivary gland samples presented with no p16Ink4a expression. Significant difference in p16Ink4a expression was observed between normal tissue, PA and CaexPA (χ2 (4)=172,19; p=0.0001). The PA clinical subgroups were also evaluated separately, revealing additional statistical relations: 'fast' PA and CaexPA differed significantly in p16Ink4a expression (χ2 (2)=8.06; p=0.01781) while 'slow' PA and CaexPA did not (χ2 (2)=3.09; p=0.2129). 3-year, 5-year and 10-year survival among p16Ink4a positive CaexPA patients was 100%, 90.56% and 60.37%, respectively, and in CaexPA patients with borderline p16Ink4a expression was 90.0%, 73.64% and 22.20%, respectively. Statistically significant difference between expression pattern and survival rate was observed (F Cox test - F (16, 24)=2.31; p=0.03075). CONCLUSIONS: Our study confirms no p16Ink4a expression in normal tissue, but reveals differences in expression between 'fast' and 'slow' PA. We suggest that p16Ink4a overexpression is connected to PA proliferation and subsequent malignant transformation to CaexPA. Borderline p16Ink4a staining correlates with worse prognosis of CaexPA.
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Adenocarcinoma , Adenoma Pleomorfo , Neoplasias das Glândulas Salivares , Adenocarcinoma/patologia , Biologia , Transformação Celular Neoplásica , Inibidor p16 de Quinase Dependente de Ciclina , Humanos , Imuno-Histoquímica , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/metabolismo , Neoplasias das Glândulas Salivares/patologiaRESUMO
Benign osteoblastoma is a rarely seen tumor of the facial bones. The authors present a case of a 30-year-old man with a tumor of the mandibular body and ramus. The histopathological diagnosis was one of osteoblastoma. Postoperative recurrence with soft tissue infiltration suggested an osteosarcoma radiologically, but the histological examination again revealed the presence of an osteoblastoma. A second recurrence occured in the pharyngo-glossal region and this time the tumor was histologically diagnosed as an osteoblastoma, but with foci of well-differentiated osteosarcoma. The patient was given a course of radiotherapy, but clinical and radiological examination 8 months later revealed lung metastases and chemotherapy was started. Unfortunately, the patient died months later. While osteoblastomas are rare, and their sarcomatous change even rarer, our experience with this case lead us to suggest that a therapeutic preventative approach, involving both chemotherapy and total excision of the tumor, is the regime to adopt with osteoblastomas which involve soft tissues and have radiological features suggesting malignancy.
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Transformação Celular Neoplásica/patologia , Neoplasias Mandibulares/patologia , Recidiva Local de Neoplasia/patologia , Osteoblastoma/patologia , Osteossarcoma/patologia , Adulto , Terapia Combinada , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Masculino , Mandíbula/patologia , Mandíbula/cirurgia , Neoplasias Mandibulares/cirurgia , Recidiva Local de Neoplasia/cirurgia , Osteoblastoma/cirurgia , Osteossarcoma/secundário , Osteossarcoma/cirurgia , Radiografia Panorâmica , Radioterapia Adjuvante , ReoperaçãoRESUMO
The report presents the results of investigations carried out in 63 patients (49 children and 14 adults) with thin glomerular basement membrane disease. Of 49 children, 13 came from nine families with family members suffering from kidney diseases (mostly manifested by haematuria). In the group of children, the most frequent initial clinical symptom (noted in 29 cases) was isolated haematuria, more rarely (in eight cases) haematuria and proteinuria, and (in seven cases) nephrotic syndrome. Isolated proteinuria was observed in another three children. In the adults, only in five patients was isolated haematuria the initial symptom of the disease; more frequently (in seven cases), they presented with isolated proteinuria. In two patients, proteinuria and haematuria were noted. In the two groups of patients, in addition to markers of thin glomerular basement membrane disease, the authors also observed markers indicative of other glomerulopathies: in seven children and four adults focal segmental glomerulosclerosis (FSGS) without any other glomerular pathologies (with the exception of thin glomerular basement membrane disease). Also in cases in which in addition to thin glomerular basement membrane disease other glomerular pathologies were present (mesangial hypercellularity, mesangial glomerulonephritis), matrix expansion was detected; this phenomenon might be considered a harbinger of glomerular sclerosis. In general, although not in each and every case, these pathologies were associated with duration of the disease.
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Membrana Basal Glomerular/patologia , Hematúria/patologia , Nefropatias/patologia , Adolescente , Adulto , Biópsia , Criança , Pré-Escolar , Matriz Extracelular/patologia , Feminino , Membrana Basal Glomerular/ultraestrutura , Hematúria/complicações , Hematúria/diagnóstico , Humanos , Lactente , Nefropatias/complicações , Nefropatias/diagnóstico , Masculino , Células Mesangiais/patologia , Pessoa de Meia-Idade , Proteinúria/etiologiaRESUMO
The study was designed to establish whether high aggressiveness of high-grade serous ovarian cancer cells (HGSOCs), which display rapid growth, advanced stage at diagnosis and the highest mortality among all epithelial ovarian cancer histotypes, may be linked with a specific pattern of mesothelial-mesenchymal transition (MMT) elicited by these cells in normal peritoneal mesothelial cells (PMCs). Experiments were performed on primary PMCs, stable and primary ovarian cancer cells, tumors from patients with ovarian cancer, and laboratory animals. Results of in vitro and in vivo tests showed that MMT triggered by HGSOCs (primary cells and OVCAR-3 line) is far more pronounced than the process evoked by cells representing less aggressive ovarian cancer histotypes (A2780, SKOV-3). Mechanistically, HGSOCs induce MMT via Smad 2/3, ILK, TGF-1, HGF, and IGF-1, whereas A2780 and SKOV-3 cells via exclusively Smad 2/3 and HGF. The conditioned medium from PMCs undergoing MMT promoted the progression of cancer cells and the effects exerted by the cells triggered to undergo MMT by the HGSOCs were significantly stronger than those related to the activity of their less aggressive counterparts. Our findings indicate that MMT in PMCs provoked by HGSOCs is stronger, proceeds via different mechanisms and has more procancerous characteristics than MMT provoked by less aggressive cancer histotypes, which may at least partly explain high aggressiveness of HGSOCs.
RESUMO
Mechanisms of transmesothelial invasion of ovarian cancer are still poorly understood. Here we examined whether this phenomenon may be determined by an expression of intercellular junctions in peritoneal mesothelial cells (PMCs). Analysis of ovarian tumors showed that cancer cells are localized below an intact layer of PMCs. The PMCs located near the invaded cancer cells displayed low expression of connexin 43, E-cadherin, occludin, and desmoglein, as well as expressed SA-ß-Gal, a marker of senescence. Experiments in vitro showed that senescent PMCs exhibited decreased levels of the four tested intercellular junctions, and that the invasion of ovarian cancer cells through the PMCs increased proportionally to the admixture of senescent cells. Intervention studies showed that the expression of connexin 43, E-cadherin, occludin, and desmoglein in senescent PMCs could be restored upon the blockade of p38 MAPK, NF-κB, AKT, JNK, HGF, and TGF-ß1. When these molecules were neutralized, the efficiency of the transmesothelial cancer cell invasion was diminished. Collectively, our findings show that the integrity of the peritoneal mesothelium, which is determined by the expression of junctional proteins, is critical for the invasion of ovarian cancer. They also indicate a mechanism by which senescent PMCs may promote the invasive potential of cancer cells.