RESUMO
A 70-year-old Japanese woman who was treated for interstitial pneumonia (IP) with steroid therapy developed cholecystitis. A serial computed-tomography (CT) imaging showed irregular thickness of the fundus wall of the gallbladder and two rapidly enlarged lymph nodes (LNs): number (no.) 12 and no. 8a. Positron-emission tomography-computed tomography (PET-CT) scan showed an abnormal uptake at the site of the gallbladder tumor and those LNs. We subsequently performed open radical cholecystectomy and LN dissection of the no. 12 and 8a LNs, following complete remission of IP. The histology showed gallbladder adenocarcinoma, with a single focus of neuroendocrine carcinoma (NEC) component of less than 30%; Ki-67 index > 80%, synaptophysin (Syn) (+), chromogranin A (CgA) (+), and clusters of differentiation (CD) 56 (+) (T2bN1M0, Stage IIIB). LN no. 8a was diffusely metastatic with NEC components. LN no. 12c, which was adjacent to the cystic duct, revealed necrosis without apparent tumor cells, but was highly suspicious for tumor necrosis. The final diagnosis was adenocarcinoma of the gallbladder with focal NEC (< 30%), which did not meet the criteria for mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN). Postoperatively, she completed 4 cycles of adjuvant chemotherapy for NEC (Cisplatin plus Etoposide), and no recurrence was observed after 12 months.
Assuntos
Adenocarcinoma , Carcinoma Neuroendócrino , Neoplasias da Vesícula Biliar , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Idoso , Carcinoma Neuroendócrino/diagnóstico por imagem , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/cirurgia , Feminino , Vesícula Biliar , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/tratamento farmacológico , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Metástase Linfática , Tomografia por Emissão de Pósitrons combinada à Tomografia ComputadorizadaRESUMO
BACKGROUND: Plasmin has recently been reported to be associated with renal fibrosis in experimental models, but its role in human renal diseases is unclear. METHODS: Fifty-seven patients with IgA nephropathy (IgAN) were evaluated retrospectively. Plasmin in their renal biopsy tissues was assessed by in situ zymography using a plasmin-sensitive synthetic peptide, and the relationships between patients' histologic or clinical parameters and their renal plasmin activity [assessed semiquantitatively by calculating the positively stained percentage of the total tubulointerstitial (TI) area] were evaluated. RESULTS: Plasmin activity was observed almost exclusively in the TI space (mainly in the interstitium and partly in the tubular epithelial cells) and was significantly stronger in patients with TI lesion (tubular atrophy/interstitial fibrosis and tubulointerstitial inflammation) than in those without TI lesion. It was significantly and positively correlated with the global glomerulosclerosis rate and significantly and negatively correlated with estimated glomerular filtration rate not only at the time of renal biopsy but also at the end of the follow-up period. Double stainings for plasmin activity and inflammatory cells, cytokeratin, or α-smooth muscle actin (α-SMA) in selected patients revealed TI infiltration of inflammatory cells, attenuated tubular epithelial expression of cytokeratin, and augmented interstitial expression of α-SMA close to upregulated plasmin activity in the TI space. CONCLUSIONS: These data suggest that TI plasmin is associated with TI inflammation leading to renal fibrosis, and can cause the decline in renal function seen in patients with IgAN. Reducing plasmin in situ may therefore be a promising therapeutic approach slowing renal fibrogenesis and improving renal function.
Assuntos
Células Epiteliais/química , Fibrinolisina/análise , Glomerulonefrite por IGA/metabolismo , Túbulos Renais/química , Actinas/análise , Adolescente , Adulto , Idoso , Biomarcadores/análise , Biópsia , Progressão da Doença , Células Epiteliais/patologia , Feminino , Fibrose , Imunofluorescência , Taxa de Filtração Glomerular , Glomerulonefrite por IGA/patologia , Glomerulonefrite por IGA/fisiopatologia , Humanos , Queratinas/análise , Túbulos Renais/patologia , Túbulos Renais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Adulto JovemRESUMO
BACKGROUND: Telomeres are repetitive DNA sequences located at the ends of chromosomes. Chromosomal and genomic instability due to telomere dysfunction has been known to play an important role in the carcinogenesis of some organs. OBJECTIVES: The aim of this study was to examine the correlation between smoking and the telomere length of human bronchial epithelial cells in individuals with and without lung cancer. PATIENTS AND METHODS: We examined 68 non-lung cancer adult autopsy cases and 24 surgically resected cases of lung squamous cell carcinoma. Telomere lengths of the basal cells of bronchial epithelium were measured using the tissue quantitative fluorescence in situ hybridization method and were expressed in normalized telomere-to-centromere ratios (NTCRs). RESULTS: The autopsied individuals included 27 current smokers (CuS), 33 never-smokers (NeS), and 8 ex-smokers (ExS). The NTCRs in the central bronchi of CuS, NeS, and ExS were 1.515, 1.372, and 1.204, respectively. The bronchial epithelial telomeres of CuS were significantly longer than those of non-CuS (NeS + ExS). When the analysis was conducted separately for females and males, a significant difference between CuS and NeS + ExS was recognized only for males. The NTCRs of the bronchial epithelium of lung cancer cases and lung cancer tissue are 1.514 and 1.385, respectively. CONCLUSIONS: Our findings suggest that smoking causes telomeric elongation in the bronchial epithelium. Therefore, it appears that the mechanism of carcinogenesis in smoking-related carcinomas may differ from that of many other carcinomas in which genetic instability due to aging-related telomeric shortening is assumed to play a role.
Assuntos
Carcinoma Broncogênico/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias Pulmonares/patologia , Mucosa Respiratória/patologia , Homeostase do Telômero , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/patologia , Estudos de Casos e Controles , Feminino , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Fumar/patologiaRESUMO
We herein report a case involving the systemic presentation of angiolymphoid hyperplasia with eosinophilia (ALHE) in association with membranous nephropathy (MN). A 34-year-old Japanese man presented with leg edema and bilateral temporal nodules. He had a history of Buerger's disease and recurrent coronary stenosis. A renal biopsy performed to assess nephrotic syndrome revealed MN. Furthermore, a temporal nodule was excised, and ALHE was diagnosed. We reevaluated the coronary and posterior tibial artery specimens obtained in his twenties and presumed that these lesions were also vascular tumors arising from ALHE. The association of ALHE and MN is quite rare.
Assuntos
Hiperplasia Angiolinfoide com Eosinofilia/complicações , Glomerulonefrite Membranosa/complicações , Adulto , Hiperplasia Angiolinfoide com Eosinofilia/diagnóstico , Humanos , MasculinoRESUMO
Pseudomonas aeruginosa is a common pathogen in nosocomial and/or healthcare-associated pneumonia, but is rare in community-acquired pneumonia. A 50-year-old previously healthy woman was taken to the emergency department because of rapidly progressing dyspnea. Chest radiograph showed consolidation of the entire right upper lobe, a finding suggestive of lobar pneumonia. The patient died of respiratory failure with bronchial bleeding, on the same day of admission. Autopsy revealed that the alveoli throughout the upper right lobe were filled with dense inflammatory cells mainly consisting of macrophages and neutrophils. Immunoreactive bacilli by using an anti-P. aeruginosa antibody were localized within macrophages accumulated in the alveoli as well in the vessel walls. Lobar pneumonia composed of dense neutrophils and bacteria-laden macrophages with total lung congestion and edema may be characteristic for community-acquired P. aeruginosa pneumonia in a healthy adult.
Assuntos
Infecções Comunitárias Adquiridas/microbiologia , Pneumonia/microbiologia , Infecções por Pseudomonas/complicações , Pseudomonas aeruginosa , Autopsia , Infecções Comunitárias Adquiridas/diagnóstico , Evolução Fatal , Feminino , Humanos , Imuno-Histoquímica , Macrófagos Alveolares/microbiologia , Macrófagos Alveolares/patologia , Pessoa de Meia-Idade , Pneumonia/diagnóstico , Infecções por Pseudomonas/diagnóstico , Pseudomonas aeruginosa/isolamento & purificaçãoRESUMO
AIM: To assess the clinicopathological significance of the histological growth pattern (HGP) and α-actinin-4 (ACTN4) expression in thyroid cancer. PATIENTS AND METHODS: We classified 83 thyroid cancer cases into infiltrative margin (IM) and pushing margin (PM) groups according to peripheral tumor margin contour and immunohistochemically determined ACTN4 expression. Correlations between clinical stage and clinicopathological characteristics were analyzed. RESULTS: IM and high ACTN4 expression were observed in 39% and 49% of cancer cases, respectively. Higher clinical stage was significantly correlated with older age, higher T and N factor, preoperative recurrent laryngeal nerve paralysis (pre-RLNP), IM, and poor prognosis. Patients with stage IV disease had significantly poorer prognosis than those with stages I-III. On multivariate analysis, older age, pre-RLNP, and IM correlated with higher clinical stages. IM was significantly correlated with high ACTN4 expression. CONCLUSION: IM, pre-RLNP, and ACTN4 expression could be novel indicators of tumor aggression and prognostic factors of thyroid cancer.
Assuntos
Actinina/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , Paralisia das Pregas Vocais/diagnóstico , Adenocarcinoma Folicular/metabolismo , Adenocarcinoma Folicular/mortalidade , Adenocarcinoma Folicular/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Medular/metabolismo , Carcinoma Medular/mortalidade , Carcinoma Medular/patologia , Carcinoma Papilar/metabolismo , Carcinoma Papilar/mortalidade , Carcinoma Papilar/patologia , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida , Neoplasias da Glândula Tireoide/mortalidade , Paralisia das Pregas Vocais/metabolismo , Adulto JovemRESUMO
Connective tissue growth factor (CTGF) has been reported to play critical roles in the tumorigenesis of several human malignancies. This study was performed to evaluate CTGF protein expression in head and neck squamous cell carcinoma (HNSCC). Surgical specimens from 76 primary HNSCC were obtained with written informed consents and the expression level of CTGF was immunohistochemically evaluated. The cytoplasmic immunoreactivity of CTGF in cancer cells was semiquantitatively classified into low and high expression. Among all 76 cases with or without neoadjuvant therapy, low CTGF showed significantly longer (P = 0.0282) overall survival (OS), but not disease-free survival (DFS) than high CTGF. Although low CTGF in patients with stage I, II and III did not result in any significant difference of the OS and DFS, stage IV HNSCC patients with low CTGF showed significantly longer OS (P = 0.032) and DFS (P = 0.0107) than those with high CTGF. These differences in stage IV cases were also confirmed using multivariate analyses. These results suggest that low CTGF in stage IV HNSCC is an independent prognostic factor, despite with or without neoadjuvant therapy.
Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Fator de Crescimento do Tecido Conjuntivo/genética , Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/terapia , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Terapia Neoadjuvante , Estadiamento de Neoplasias , Prognóstico , Taxa de SobrevidaRESUMO
We report a case in which renal biopsies were performed 4 years apart in a woman with a prolonged human parvovirus B19 (HPB19) infection. When she was 29 years old the first biopsy, performed because of microscopic hematuria and mild proteinuria, showed endocapillary and mesangial proliferative glomerulonephritis in light microscopy as well as deposits of immunoglobulins (Igs) and complement C3 on capillary walls. Mesangial, intramembranous, and subepithelial hump-like electron dense deposits were seen in electron microscopy. The principal differential diagnoses, acute poststreptococcal glomerulonephritis and lupus nephritis, were unlikely, and her serological positivity for IgM antibody for HPB19 made us diagnose acute glomerulonephritis associated with HPB19 infection. The second biopsy, performed 4 years later because of persistent proteinuria and prolonged positivity for IgM antibody for HPB19, showed membranoproliferative glomerulonephritis (MPGN) with mesangial interposition and with thickening and double contours of glomerular basement membrane. In tissues obtained in both biopsies, HPB19 DNA was detected by polymerase chain reaction. HPB19 infection has been widely known to cause various glomerular diseases. This case reveals that acute endocapillary proliferative glomerulonephritis can change into MPGN during prolonged HPB19 infection.
Assuntos
Glomerulonefrite Membranoproliferativa/virologia , Rim/virologia , Infecções por Parvoviridae/complicações , Parvovirus B19 Humano/isolamento & purificação , Adulto , Anticorpos Antivirais/sangue , Biópsia , DNA Viral/isolamento & purificação , Diagnóstico Diferencial , Progressão da Doença , Feminino , Glomerulonefrite Membranoproliferativa/diagnóstico , Glomerulonefrite Membranoproliferativa/imunologia , Humanos , Imunoglobulina M/sangue , Rim/imunologia , Rim/patologia , Infecções por Parvoviridae/diagnóstico , Infecções por Parvoviridae/virologia , Parvovirus B19 Humano/genética , Parvovirus B19 Humano/imunologia , Valor Preditivo dos Testes , Fatores de TempoRESUMO
Overexpression of fatty acid synthase (FASN), which is a key enzyme responsible for the endogenous synthesis of fatty acids, and its association with multistep progression have been demonstrated in various human malignant tumors. We aimed to clarify the potential role of FASN overexpression in the development and progression of adult testicular germ cell tumors (TGCTs). From the primary sites of a cohort of 113 TGCT cases, we obtained 221 histological components: 53 intratubular germ cell neoplasias, unclassified (IGCNUs), 84 seminomas, 32 embryonal carcinomas, seven choriocarcinomas, 21 yolk sac tumors, and 24 teratomas. Samples were analyzed for overexpression of FASN by immunohistochemistry. Intensities of immunoreactivity and the fraction of positive cells were classified into each four categories (intensity, 0 to 3; fraction, 0-10 % = 1, 11-50 % = 2, 51-80 % = 3, and >80 % = 4). The overall score was determined by multiplication of both scores and overall scores greater than 6 were considered FASN overexpression. On a component basis, FASN overexpression was detected in 8 % of seminomas but not in IGCNUs (0 %) and was detected frequently in non-seminomatous germ cell tumors (NSGCTs) (88 % of embryonal carcinomas, all choriocarcinomas, 81 % of yolk sac tumors, and 54 % of teratomas). There were no cases of a mixed tumor (i.e., a tumor with multiple histological components) that overexpressed FASN in seminoma components but not in co-existing NSGCT components, suggesting sequential progression. Our immunohistochemical data suggest that FASN overexpression occurs as a late event during the progression from IGCNUs/seminomas to NSGCTs.
Assuntos
Ácido Graxo Sintases/biossíntese , Neoplasias Embrionárias de Células Germinativas/enzimologia , Neoplasias Testiculares/enzimologia , Adolescente , Adulto , Idoso , Progressão da Doença , Ácido Graxo Sintases/análise , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Análise Serial de Tecidos , Adulto JovemRESUMO
Differentiating nonspecific interstitial pneumonia (NSIP) from usual interstitial pneumonia (UIP) is important for the determination of both treatment and prognosis. Using two-dimensional fluorescence difference gel electrophoresis (2D-DIGE), we examined 8 UIPs, 8 NSIPs, and 30 normal lung tissues. Comparisons with control in 2D-DIGE showed that (a) in UIP, nine protein spots were significantly upregulated and seven were significantly downregulated, (b) in NSIP, four protein spots were significantly upregulated and nine were significantly downregulated. The detected proteins were analyzed by MALDI-TOF mass spectrometry, allowing qualitative differences in vimentin subtypes to be characterized. One vimentin subtype was upregulated in UIP, while another one was downregulated in NSIP (vs. control). These different characteristics were partially supported by the results of Western blot analysis. Our immunohistochemistry revealed vimentin expression within fibroblasts (a) in fibroblastic foci in UIP and (b) in fibrotic alveolar walls in NSIP. Differences in vimentin subtypes may provide useful biomarkers for separating NSIP from UIP, alongside differences in histological characteristics.
Assuntos
Fibrose Pulmonar Idiopática/diagnóstico , Vimentina/biossíntese , Biomarcadores/análise , Western Blotting , Diagnóstico Diferencial , Eletroforese em Gel Bidimensional , Humanos , Fibrose Pulmonar Idiopática/metabolismo , Imuno-Histoquímica , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/metabolismo , Proteômica , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
BACKGROUND: The therapeutic effect of tonsillectomy for immunoglobulin A nephropathy (IgAN) has been widely recognized, but the mechanism by which tonsillar immunity leads to glomerulonephritis has been unclear. We investigated subtypes and localization of dendritic cells (DCs) in tonsils and looked for relationships between the tonsillar DCs and the clinical features and renal histological changes of patients with IgAN. METHODS: We examined tonsils from 33 IgAN patients, using as control tonsillar specimens from subjects without glomerulonephritis. Five distinct markers of DCs (CD303, CD1c, CD209, CD208 and CD1a) were analyzed by immunohistochemistry and flow cytometry. The mRNA levels of these DC markers were evaluated using real-time polymerase chain reaction. The clinical data and histological results obtained evaluating renal biopsy tissues were statistically compared with immunological data. RESULTS: Of the five subtypes of DCs, CD208(+) DCs were significantly increased in the tonsils of IgAN patients compared with that of controls. Furthermore, the number of CD208(+) DCs in the tonsils was positively and linearly correlated with the proportion of crescentic glomeruli in renal biopsy tissues and with the urinary protein level. Only few CD208(+) cells, however, were found in the kidney biopsy specimens of IgAN patients. CONCLUSIONS: These observations suggest that increased CD208(+) DCs in tonsils may play a directive role in the pathogenesis of IgAN. The present results support the therapeutic significance of tonsillectomy for IgAN patients.
Assuntos
Células Dendríticas/imunologia , Glomerulonefrite por IGA/imunologia , Proteínas de Membrana Lisossomal/metabolismo , Proteínas de Neoplasias/metabolismo , Tonsila Palatina/imunologia , Adulto , Western Blotting , Estudos de Casos e Controles , Células Dendríticas/metabolismo , Células Dendríticas/patologia , Feminino , Citometria de Fluxo , Glomerulonefrite por IGA/metabolismo , Glomerulonefrite por IGA/cirurgia , Humanos , Técnicas Imunoenzimáticas , Rim/imunologia , Rim/metabolismo , Rim/patologia , Masculino , Tonsila Palatina/metabolismo , Tonsila Palatina/patologia , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , TonsilectomiaRESUMO
Among adult testicular germ cell tumors, the pathogenesis of embryonal carcinoma remains a matter of debate. Some studies suggest a single consecutive progression from intratubular germ cell neoplasia, unclassified (IGCNU), to seminoma and then to embryonal carcinoma; others suggest that seminoma and embryonal carcinoma derive independently from IGCNU. This allelotyping study aimed to clarify the genetic relationship between embryonal carcinoma components and coexisting seminoma and/or IGCNU components. From a cohort of 18 patients with embryonal carcinoma, 11 coexisting seminoma components and 14 coexisting IGCNUs were identified. DNA isolated from each laser-microdissected tissue was subjected to polymerase chain reaction and loss of heterozygosity (LOH) analysis, using 20 polymorphic markers located on 12 chromosome arms (3q, 5q, 6p, 9p, 10q, 11p, 12p, 12q, 13q, 17p, 17q, and 18q). The concordance rate for allelic patterns was 82% between IGCNU and the coexisting seminoma components, 71% between IGCNU and the coexisting embryonal carcinoma components, and 80% between seminoma components and the coexisting embryonal carcinoma components. Estimation of probability indicated that these events were very unlikely to have occurred by chance. The total frequency of LOH increased progressively from IGCNU to seminoma and then to embryonal carcinoma, with statistically significant differences. In 7 cases with 3 histologic components, 28 chromosomal loci that showed LOH in the seminoma and embryonal carcinoma components were identified, and 15 (54%) retained heterozygosity in the coexisting IGCNUs. These findings suggest that a consecutive progression from IGCNU to seminoma, and ultimately, to embryonal carcinoma mainly occurred in the testicular germ cell tumor cases.
Assuntos
Carcinoma Embrionário/genética , Genótipo , Lesões Pré-Cancerosas/genética , Seminoma/genética , Neoplasias Testiculares/genética , Adulto , Biomarcadores Tumorais/genética , Carcinoma Embrionário/patologia , Análise Mutacional de DNA , DNA de Neoplasias/análise , Progressão da Doença , Humanos , Microdissecção e Captura a Laser , Perda de Heterozigosidade , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/patologia , Seminoma/patologia , Neoplasias Testiculares/patologia , Adulto JovemRESUMO
We examined the potential role of cell-cycle dysregulation in the development and histological progression of adult testicular germ cell tumors (TGCTs). Expressions of p27(Kip1) -interacting cell-cycle regulators (down-regulation of p27(Kip1) and overexpression of Skp2, Cks1, cyclin A, and cyclin E) and Ki-67 labeling index (LI) were immunohistochemically examined in histological components of 50 intratubular germ cell neoplasms, unclassified (IGCNUs); 74 seminomas; and 25 embryonal carcinomas, identified from 88 patients. Altered expression of p27(Kip1) , Skp2, Cks1, cyclin A, and cyclin E was observed in 20%, 12%, 16%, 10%, and 24% of IGCNUs; 26%, 36%, 27%, 89%, and 23% of seminomas; and 48%, 68%, 56%, 100%, and 60% of embryonal carcinomas, respectively. A significant difference in the frequency of Skp2 and cyclin A overexpression was observed between IGCNUs and seminomas. Significantly more frequent alterations of Skp2, Cks1, and cyclin E and p27(Kip1) were detected in embryonal carcinomas than in seminomas. Alterations of all cell-cycle regulators were significantly more frequent in embryonal carcinomas than in IGCNUs. The mean Ki-67 LI significantly increased from IGCNU (21.2%) through seminoma (34.7%) to embryonal carcinoma (54.2%). These results suggest that alterations of the p27(Kip1) -interacting cell-cycle regulators are common in TGCTs and may be involved in their histological progression.
Assuntos
Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Testiculares/genética , Adolescente , Adulto , Idoso , Quinases relacionadas a CDC2 e CDC28/genética , Quinases relacionadas a CDC2 e CDC28/metabolismo , Carcinoma Embrionário/genética , Carcinoma Embrionário/patologia , Ciclo Celular , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Ciclina A/genética , Ciclina A/metabolismo , Ciclina E/genética , Ciclina E/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/genética , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Células Germinativas/metabolismo , Células Germinativas/patologia , Humanos , Imuno-Histoquímica , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/metabolismo , Proteínas Quinases Associadas a Fase S/genética , Proteínas Quinases Associadas a Fase S/metabolismo , Seminoma/genética , Seminoma/patologia , Adulto JovemRESUMO
Bacteremia due to Mycobacterium massiliense is rare. We present here the case of a 58-year-old man with chronic myelogenous leukemia complicated by bacteremia caused by M. massiliense. The microorganisms were identified as M. massiliense by sequencing analysis, having initially been misdiagnosed as M. abscessus by DNA-DNA hybridization.
Assuntos
Bacteriemia/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Infecções por Mycobacterium/diagnóstico , Mycobacterium/isolamento & purificação , Bacteriemia/microbiologia , Bacteriemia/patologia , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium/classificação , Mycobacterium/genética , Infecções por Mycobacterium/microbiologia , Infecções por Mycobacterium/patologia , Reação em Cadeia da Polimerase , RNA Ribossômico 16S/genética , Análise de Sequência de DNARESUMO
Noc2, a putative Rab effector, contributes to secretory-granule exocytosis in neuroendocrine and exocrine cells. Here, using two-photon excitation live-cell imaging, we investigated its role in Ca(2+)-dependent zymogen granule (ZG) exocytosis in pancreatic acinar cells from wild-type (WT) and Noc2-knockout (KO) mice. Imaging of a KO acinar cell revealed an expanded granular area, indicating ZG accumulation. In our spatiotemporal analysis of the ZG exocytosis induced by agonist (cholecystokinin or acetylcholine) stimulation, the location and rate of progress of ZG exocytosis did not differ significantly between the two strains. ZG exocytosis from KO acinar cells was seldom observed at physiological concentrations of agonists, but was normal (vs. WT) at high concentrations. Flash photolysis of a caged calcium compound confirmed the integrity of the fusion step of ZG exocytosis in KO acinar cells. The decreased ZG exocytosis present at physiological concentrations of agonists raised the possibility of impaired elicitation of calcium spikes. When calcium spikes were evoked in KO acinar cells by a high agonist concentration: (a) they always started at the apical portion and traveled to the basal portion, and (b) calcium oscillations over the 10 µM level were observed, as in WT acinar cells. At physiological concentrations of agonists, however, sufficient calcium spikes were not observed, suggesting an impaired [Ca(2+)](i)-increase mechanism in KO acinar cells. We propose that in pancreatic acinar cells, Noc2 is not indispensable for the membrane fusion of ZG per se, but instead performs a novel function favoring agonist-induced physiological [Ca(2+)](i) increases.
Assuntos
Células Acinares/metabolismo , Cálcio/metabolismo , Pâncreas/metabolismo , Proteínas/metabolismo , Vesículas Secretórias/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Animais , Sinalização do Cálcio/fisiologia , Exocitose/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular , Fusão de Membrana/fisiologia , Camundongos , Camundongos Knockout , Pâncreas Exócrino/metabolismoRESUMO
AIMS: Actinin-4, encoded by the ACTN4 gene located on chromosome 19q13.2, enhances cell motility by bundling the actin cytoskeleton. We assessed how ACTN4/actinin-4 alterations contribute to the tumorigenesis of ovarian clear-cell adenocarcinomas (CCAs). METHODS AND RESULTS: Fluorescence in-situ hybridization analysis demonstrated that ACTN4 amplification (≥4 ACTN4 copies in ≥40% of cells) occurred in 27 (33%) of 81 CCAs and genomic gains of ACTN4 were associated strongly with immunohistochemical actinin-4 overexpression, poorly differentiated tumour histology and shorter patient survival (all P < 0.05). From the 27 ACTN4-amplified CCAs, 23 tumours with adjacent putative precursor lesions were selected and examined for ACTN4/actinin-4 alterations with respect to their intratumoral heterogeneity. In this selected cohort, none of the precursors lacking cytological atypia exhibited gains of ACTN4 or actinin-4 overexpression; 50% of the atypical endometrioses and 75% of the borderline CCAFs showed low-level gains of ACTN4 and actinin-4 overexpression, respectively. In 12 of 23 ACTN4-amplified CCAs, intratumoral heterogeneity for ACTN4 alterations was documented in carcinomatous components; the better differentiated carcinoma components exhibited fewer alterations than those with poorly differentiated histology. CONCLUSION: Accumulative genomic gains of ACTN4, causing actinin-4 protein overexpression, drive the development and progression of ovarian CCAs with high-grade histology.
Assuntos
Actinina/genética , Actinina/metabolismo , Adenocarcinoma de Células Claras/genética , Adenocarcinoma de Células Claras/patologia , Amplificação de Genes , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Adenocarcinoma de Células Claras/etiologia , Adenocarcinoma de Células Claras/metabolismo , Adenofibroma/genética , Adenofibroma/metabolismo , Adenofibroma/patologia , Adulto , Idoso , Progressão da Doença , Endometriose/genética , Endometriose/metabolismo , Endometriose/patologia , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Neoplasias Ovarianas/etiologia , Neoplasias Ovarianas/metabolismo , Regulação para CimaRESUMO
A 53-year-old woman with a history of dyslipidemia presented with medium-grade proteinuria and several years of progressive renal dysfunction. Renal biopsy showed diffuse and global Kimmelstiel-Wilson nodule like nodular mesangial sclerosis, but she had no history of diabetes mellitus, no diabetic retinopathy and normal oral glucose tolerance. Congo red staining was negative, and immunofluorescence staining showed no immunoglobulin deposition including kappa or lambda light chains. Electron microscopy showed no electron dense deposits or organized deposits. Thus, we diagnosed idiopathic nodular glomerulosclerosis (ING). ING is a recently established clinicopathologic disease entity linked to longstanding cigarette smoking and hypertension. Obesity is also listed as a contributing factor. However, none of these factors was documented in this case. This is a valuable case of ING that suggests the existence of as-yet unknown causative factors of ING other than smoking, hypertention or obesity.
RESUMO
Our previous study demonstrated that, among ovarian carcinomas, amplification of the MET gene and overexpression of MET specifically and commonly occur in clear-cell adenocarcinoma histology. This study was conducted to address how these alterations contribute to development and progression of this highly chemoresistant form of ovarian cancer. We histologically reviewed 21 previously described MET amplification-positive clear-cell adenocarcinoma cases, and selected 11 tumors with synchronous endometriosis and 2 tumors with adjacent clear-cell adenofibroma (CCAF) components. Using double in situ hybridization and immunohistochemistry, copy number alterations of the MET gene and levels of MET protein expression were analyzed in these putative precursor lesions and the corresponding invasive carcinoma components in this selected cohort. All of the non-atypical precursor lesions analyzed (ie, non-atypical endometrioses and the benign CCAFs) were negative for MET gain. However, low-level (≥3 MET copies in ≥10% and ≥4 MET copies in 10-40% of tumor cells) gain of MET was detected in 4 (40%) of the 10 atypical endometrioses and 1 of the 2 borderline CCAFs. Moreover, high-level (≥4 MET copies in ≥40% of tumor cells) gain of MET were detected in five (50%) of the atypical endometrioses. In 4 (31%) of the 13 cases enrolled, intratumoral heterogeneity for MET gain was documented in invasive carcinoma components, wherein all the relatively differentiated carcinoma components showed low-level gain of MET and all the corresponding poorly differentiated carcinomas showed high-level gain. The overall incidence of MET overexpression gradually increased from the precursors of non-atypical form (0%), through those of atypical form (67%) and the relatively differentiated carcinoma components (92%), to the poorly differentiated carcinoma components (100%). These results suggest that accumulative MET gene copy number alterations causing MET overexpression are associated with higher tumor grade and might drive the development and progression of the MET amplification-positive ovarian clear-cell adenocarcinoma.
Assuntos
Adenocarcinoma de Células Claras/genética , Adenofibroma/genética , Biomarcadores Tumorais/genética , Transformação Celular Neoplásica/genética , Endometriose/genética , Amplificação de Genes , Dosagem de Genes , Neoplasias Ovarianas/genética , Lesões Pré-Cancerosas/genética , Proteínas Proto-Oncogênicas c-met/genética , Adenocarcinoma de Células Claras/química , Adenocarcinoma de Células Claras/patologia , Adenofibroma/metabolismo , Adenofibroma/patologia , Biomarcadores Tumorais/análise , Diferenciação Celular , Transformação Celular Neoplásica/química , Transformação Celular Neoplásica/patologia , Distribuição de Qui-Quadrado , Progressão da Doença , Endometriose/metabolismo , Endometriose/patologia , Feminino , Humanos , Imuno-Histoquímica , Hibridização In Situ , Japão , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Ovarianas/química , Neoplasias Ovarianas/patologia , Lesões Pré-Cancerosas/química , Lesões Pré-Cancerosas/patologia , Prognóstico , Proteínas Proto-Oncogênicas c-met/análiseRESUMO
BACKGROUND: This study was designed to clarify retrospectively the clinical significance of occult metastases in both sentinel lymph nodes (SLNs) and non-SLNs in patients with early breast cancer. METHODS: A total of 109 (80.1%) of 136 women with breast cancer who had consecutively undergone SLN biopsy (176 lymph nodes) were intraoperatively diagnosed as being free of SLN involvement. SLNs were routinely examined by hematoxylin-eosin (HE) staining of one to four frozen sections per node. Sixty-four (58.7%) of these patients also underwent backup axillary dissection. For the 109 patients, all formalin-fixed, paraffin-embedded tissues of SLNs and non-SLNs were entirely cut into 5-µm-thick sections. All serial step sections at 85-µm intervals were stained with HE and immunohistochemistry with pancytokeratin. RESULTS: Occult metastases in SLNs and non-SLNs were detected in 25 (23%) and 10 (16%) patients, respectively. The presence of occult SLN metastasis was marginally correlated with T-factor (P=0.06), and predictive factors for occult non-SLN metastases were tumor nuclear grade (P=0.039). With a median follow-up of 86 months, disease-free survival (P=0.3) or overall survival (P=0.8) did not differ between the patients with and without occult SLN metastases, regardless of backup axillary lymph node dissection. CONCLUSIONS: SLN or non-SLN occult metastases detected by serial step sections at 85-µm intervals did not have significant prognostic implications.
Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/secundário , Carcinoma Lobular/patologia , Carcinoma Lobular/secundário , Linfonodos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Axila , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/mortalidade , Carcinoma Lobular/terapia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Metástase Linfática , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela , Análise de SobrevidaRESUMO
ARID1A is a recently identified tumor suppressor gene that is mutated in â¼50% of ovarian clear-cell carcinomas. This mutation is associated with loss of ARID1A protein expression as assessed by immunohistochemistry. The present study aimed at determining the timing of the loss of ARID1A protein expression during the development of ovarian clear-cell carcinoma and assessing its relevance in correlation to PIK3CA gene mutations. A total of 42 clear-cell carcinoma cases with adjacent putative precursor lesions (endometriosis-associated carcinoma cases (n=28) and (clear-cell) adenofibroma-associated carcinoma cases (n=14)) were selected and subjected to immunohistochemical analysis for ARID1A protein expression and direct genomic DNA sequencing of exons 9 and 20 of the PIK3CA gene. ARID1A immunoreactivity was deficient in 17 (61%) of the 28 endometriosis-associated carcinomas and 6 (43%) of the 14 adenofibroma-associated carcinomas. Among the precursor lesions adjacent to the 23 ARID1A-deficient carcinomas, 86% of the non-atypical endometriosis (12 of 14) and 100% of the atypical endometriosis (14 of 14), benign (3 of 3), and borderline (6 of 6) clear-cell adenofibroma components were found to be ARID1A deficient. In contrast, in the 19 patients with ARID1A-intact carcinomas, all of the adjacent precursor lesions retained ARID1A expression regardless of their types and cytological atypia. Analysis of 22 solitary endometrioses and 10 endometrioses distant from ARID1A-deficient carcinomas showed that all of these lesions were diffusely immunoreactive for ARID1A. Among the 42 clear-cell carcinomas, somatic mutations of PIK3CA were detected in 17 (40%) tumors and majority (71%) of these were ARID1A-deficient carcinomas. These results suggest that loss of ARID1A protein expression occurs as a very early event in ovarian clear-cell carcinoma development, similar to the pattern of PIK3CA mutation recently reported by our group, and frequently coexists (not mutually exclusive) with PIK3CA mutations.