ALDA WAKAMATSU
Índice h a partir de 2011
11
Projetos de Pesquisa
Unidades Organizacionais
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina
36 resultados
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- Impact of a cell cycle and an extracellular matrix remodeling transcriptional signature on tumor progression and correlation with EZH2 expression in meningioma(2022) PEREIRA, Benedito Jamilson Araujo; LERARIO, Antonio Marcondes; SOLA, Paula Rodrigues; LAURENTINO, Talita de Sousa; MOHAN, Dipika R.; ALMEIDA, Antonio Nogueira de; AGUIAR, Paulo Henrique Pires de; PAIVA, Wellingson da Silva; WAKAMATSU, Alda; TEIXEIRA, Manoel Jacobsen; OBA-SHINJO, Sueli Mieko; MARIE, Suely Kazue NagahashiOBJECTIVE The authors searched for genetic and transcriptional signatures associated with tumor progression and recurrence in their cohort of patients with meningiomas, combining the analysis of targeted exome, NF2-LOH, transcrip-tome, and protein expressions. METHODS The authors included 91 patients who underwent resection of intracranial meningioma at their institution between June 2000 and November 2007. The search of somatic mutations was performed by Next Generation Sequenc-ing through a customized panel and multiplex ligation-dependent probe amplification for NF2 loss of heterozygosity. The transcriptomic profile was analyzed by QuantSeq 3 ' mRNA-Seq. The differentially expressed genes of interest were validated at the protein level analysis by immunohistochemistry.RESULTS The transcriptomic analysis identified an upregulated set of genes related to metabolism and cell cycle and downregulated genes related to immune response and extracellular matrix remodeling in grade 2 (atypical) meningio-mas, with a significant difference in recurrent compared with nonrecurrent cases. EZH2 nuclear positivity associated with grade 2, particularly with recurrent tumors and EZH2 gene expression level, correlated positively with the expres-sion of genes related to cell cycle and negatively to genes related to immune response and regulation of cell motility. CONCLUSIONS The authors identified modules of dysregulated genes in grade 2 meningiomas related to the activation of oxidative metabolism, cell division, cell motility due to extracellular remodeling, and immune evasion that were predic-tive of survival and exhibited significant correlations with EZH2 expression.
conferenceObject A Lower Ki 67 Labelling Index (LI) Cut-Point Improves the Prognostic Assessment and Might Aid in the Diagnosis of Adult Adrenocortical Tumors(2018) MARTINS FILHO, Sebastiao N.; ALMEIDA, Madson Q.; SOARES, Ibere C.; WAKAMATSU, Alda; ALVES, Venancio; FRAGOSO, Maria C.; ZERBINI, Maria- IMMUNOHISTOCHEMICAL ASSESSMENT OF LYMPHATIC VESSELS IN HUMAN LIVERS WITH CHRONIC HEPATITIS C - RELATION TO HISTOLOGICAL VARIABLES(2022) ASSATO, Aline Kawassaki; PASINATO, Ana Paula Beltrame Farina; CIRQUEIRA, Cinthya dos Santos; WAKAMATSU, Alda; ALVES, Venâncio Avancini FerreiraABSTRACT Background Viral hepatitis C is a significant public health challenge. The disease may remain clinically silent in both acute and chronic forms, and chronic infections may progress to advanced disease such as cirrhosis and hepatocellular carcinoma, requiring costly treatment, compromising the patient’s quality of life and even leading to death. For this reason, it is one of the most frequent indications for liver transplantation. Although treatment with direct-acting antivirals represents remarkable progress, many patients are still infected and even those who cleared the viral infection must be followed due to their previous hepatic lesions, especially regarding the disturbances of lobular architecture and the sanguineal and lymphatic vessels. Objective To assess immunohistochemical aspects of lymphatic sprouts and mature lymphatic vascularity with histological variables of liver injury attributable to hepatitis C virus (HCV) and fatty disease. Methods The present study included 72 liver biopsies of cases with chronic hepatitis C. Morphologic changes reflecting “staging” and “activity” were analyzed. Immunohistochemical reactions were performed with monoclonal antibody D2-40 anti-podoplanin. Major histological variables were also semiquantified so as to enable the search for possible associations among histological and Immunohistochemical criteria, as well as with genotypes 1 and 3 of HCV. Results Histological findings showed that the different degrees of strutural changes were well represented in this casuistic. Intralobular/parenchymal necro-inflammatory activity was predominantly mild to moderate. Most cases did not show major evidences of fatty disease, which was found significantly higher in cases infected with HCV genotype 3. The amount of portal lymphatic sprouts increased along with the progression of structural changes, maximal at cirrhosis. Portal lymphatic sprouts as well as portal mature lymphatic vessels also showed an increase parallel to the increase in the degree of portal/septal inflammatory infiltrate. In the present study, no significant association was found between the proportion of portal lymphatic sprouts or portal mature lymphatic vessels and the degree of periportal/periseptal activity. No significant relations were detected between lymphatic sprouts/mature vessels and periportal or parenchymal inflammatory activity, nor with infections due to HCV genotype 1 or 3. Conclusion Visualization and semiquantitation of sprouts and mature lymphatic vessels were clearly yielded by Immunohistochemical staining with monoclonal antibody D2-40. The amount of lymphatics was increased along fibrogenic process, significantly related to progression of liver disease and maximal at cirrhosis. No significant relations were detected with necro-inflammatory activity at interface or in the parenchyma.
- A phenotypical map of disseminated hepatocellular carcinoma suggests clonal constraints in metastatic sites(2019) MARTINS-FILHO, Sebastiao N.; ALVES, Venancio A. F.; WAKAMATSU, Alda; MAEDA, Miho; CRAIG, Amanda J.; ASSATO, Aline K.; VILLACORTA-MARTIN, Carlos; D'AVOLA, Delia; LABGAA, Ismail; CARRILHO, Flair J.; THUNG, Swan N.; VILLANUEVA, AugustoAims Access to tissue in patients with hepatocellular carcinoma (HCC) is limited compared to other malignancies, particularly at advanced stages. This has precluded a thorough characterisation of molecular drivers of HCC dissemination, particularly in relation to distant metastases. Biomarker assessment is restricted to early stages, and paired primary-metastatic comparisons between samples from the same patient are difficult. Methods and results We report the evaluation of 88 patients with HCC who underwent autopsy, including multiregional sampling of primary and metastatic sites totalling 230 nodules analysed. The study included morphological assessment, immunohistochemistry and mutation status of the TERT promoter, the most frequently mutated gene in HCC. We confirm a strong predilection of HCC for lung dissemination, including subclinical micrometastases (unrecognised during imaging and macroscopic examinations) in 30% of patients with disseminated disease. Size of dominant tumour nodule; multinodularity; macrovascular invasion; high histological, nuclear and architectural grades; and cellular crowding were associated with the presence of extrahepatic metastasis. Among the immunohistochemistry markers tested, metastatic nodules had significantly higher K19 and EpCAM expression than primary liver tumours. Morphological and immunohistochemical features showed that metastatic HCC could be traced back to the primary tumour, sometimes to a specific hepatic nodule. Conclusions This study suggests limited heterogeneity in metastatic sites compared to primary tumour sites.
- Activation of EGFR signaling from pilocytic astrocytomas to glioblastomas(2014) CARVALHO, Priscila O.; UNO, Miyuki; OBA-SHINJO, Sueli M.; ROSEMBERG, Sergio; WAKAMATSU, Alda; SILVA, Clemar C. da; TEIXEIRA, Manoel J.; MARIE, Suely K. N.Introduction: EGFR analyses allow for better correlation between genotype and phenotype in astrocytomas and represent an attractive therapeutic target. Most studies emphasize analyses of EGFR in glioblastomas (GBMs) but do not analyze all grades of astrocytomas (from pilocytic to GBM). The purpose of our study was to evaluate the status of EGFR (expression, deletion, and amplification) and EGFR protein expression in all grades of astrocytomas. Patients and methods: We analyzed a total of 145 surgical tumor specimens that included: 22 pilocytic astrocytomas, 22 grade II astrocytomas, 17 grade III astrocytomas and 84 GBMs. The specimens were compared to 17 non-neoplastic brain tissues obtained from epilepsy surgery. EGFR expression, EGFR amplification and EGFRvIII analyses were performed by quantitative real-time PCR, and protein expression was evaluated by immunohistochemistry. Results: EGFR relative overexpression and EGFR amplification were observed, respectively, in 50% and 20% of astrocytomas, while EGFRvIII was only found in GBMs (34.5%, p=0.005). Amongst EGFR-amplified GBM cases, 59% also presented EGFRvIII (p<0.001). Cytoplasmic accumulation of EGFR protein was detected in 75% of astrocytomas, and 21% of the astrocytomas showed nuclear localization (p=0.003). Conclusions: EGFR alterations were found in all grades of astrocytomas, from pilocytic to GBMs, while EGFRvIII was exclusively found in GBMs. These findings provide important information on the mechanisms involved in the progression of astrocytomas for determining whether EGFR status can be used for effective and specific therapy.
- Immunohistochemical Assessment of the Expression of Biliary Transportation Proteins MRP2 and MRP3 in Hepatocellular Carcinoma and in Cholangiocarcinoma(2019) CIRQUEIRA, Cinthya Santos; FELIPE-SILVA, Aloisio Sousa; WAKAMATSU, Alda; MARINS, Lidiane Vieira; ROCHA, Eziel Cavalcanti; MELLO, Evandro Sobroza de; ALVES, Venancio Avancini FerreiraMultidrug resistance-associated protein 2 (MRP2) is a multi-specific organic anion transporter predominantly expressed in the canalicular membrane of hepatocytes, epithelial cells from gallbladder and apical membranes of proximal tubular kidney epithelium whereas multidrug resistance-associated protein 3 (MRP3) is present in the basolateral membrane of hepatocytes and cholangiocytes. This study aims to detect the expression of these transporters in hepatocellular carcinoma (HCC) and in cholangiocarcinoma (CC), searching for evidences for future studies on differential diagnosis and on clinical essays. The immunohistochemical reactivity (IHC) of these transporters was assessed in tissue microarrays of 80 HCC and 56 CC cases using monoclonal antibodies and compared with anatomopathological (AP) variables. The positivity of MRP2 was observed in 92.3% of HCC and in 96.3% of CC. The detection of high MRP2 expression in HCC was not significantly different (p > 0.05) according to the size, number of nodules architectural pattern and growth pattern of HCC and CC. Regarding histological grades, 22/22 well moderately differentiated HCC versus 50/56 poorly differentiated HCC were positive for MRP2. A trend for lower expression in poor differentiation HCC was found. And 50/50 well/moderately differentiated CC versus 2/4 poorly/undifferentiated CC were positive for MRP2. This result showed a reduced expression (p = 0,0004) in poorly differentiated CC. MRP3 positivity was observed in 18.8% of HCC and was not significantly different according to AP parameters. MRP3 was expressed in 44.5% CC, with a trend for lower expression in less differentiated CC and significantly lower rates in the ductular histological subtype (p = 0.023). The high expression of MRP2 in HCC and in CC is conserved regardless most of the anatomopathological parameters, except for a trend of lower expression in less differentiated HCC and CC. The observation of lower MRP3 expression in less differentiated CC and, especially, in the histological subtype with expression of hepatic progenitor cell phenotypes leads to future opportunities to evaluate the expression of this marker in cholangiocarcinomas.
- Muscle Fiber Type Composition, Fiber Diameter, Capillary Density in Temporalis and Masseter Muscles and Correlation with Bite Force(2013) GUIMARAES, Thatiana Bastos; FERREIRA, Mariana Brandao; WAKAMATSU, Alda; OLIVEIRA, Stanley Reis; GUIMARAES, Antonio Sergio; GALDAMES, Ivan Suazo; MARIE, Suely NagahashiThe jaw muscles are essential components in the stomatognatic system. Their complex architecture allows them to execute several motor tasks. One of the structural peculiarities is the presence of hybrid and neonatal fibers. We studied the differences of the fiber-type in masseter and temporalis muscles along the first to nineth decades in both genders. Seventy-four (74) samples were analyzed by immunohistochemistry. Slow and fast muscle fibers distribution was similar in both muscles in both genders. Hybrid fiber was observed in all decades, and its frequency decreased significantly (p<0.001) with aging in masseter. Neonatal myosin expression was observed in all decades, its expression was more frequent in masseter (p=0.01), and males in temporalis (p=0.025). Decrease of the cross sectional area of fast and slow fibers, and decrease of capillary density were detected with aging. These morpho-immunohistochemical alterations on masseter and temporalis muscles correlated to the decrease in bite force with aging.
- Angiogenesis and expression of PDGF-C, VEGF, CD105 and HIF-1 alpha in human glioblastoma(2014) CLARA, Carlos Afonso; MARIE, Suely K. N.; ALMEIDA, Jose Reynaldo Walther de; WAKAMATSU, Alda; OBA-SHINJO, Sueli Mieko; UNO, Miyuki; NEVILLE, Munro; ROSEMBERG, SergioGlioblastoma (GBM), the most frequent and aggressive brain tumor, is characterized by marked angiogenesis directly related to invasiveness and poor prognosis. Hypoxia is considered to be an important stimulus for angiogenesis by inducing hypoxia-inducible factor 1-alpha (HIF-1 alpha) overexpression that activates platelet-derived growth factor (PDGF) and VEGF. The aim of this study is to analyze the expression of PDGF-C, VEGFin endothelial and tumor cells of GBM and their relation to HIF-1 alpha expression. Two hundred and eight GBM cases were studied by tissue microarray immunohistochemical preparation. Expression of HIF-1 alpha, VEGF and PDGF-C was observed in 184 (88.5%), 131 (63%) and 160 (76.9%) tumor cases, respectively. The numbers of vessels were quantified by CD34, PDGF-C, VEGF and CD105 staining, and were in median 20, 16, 5 and 6, respectively. The GBMs that showed positive or negative expression for HIF-1 alpha showed a median vascular density of 30 and 14, respectively, for CD34 (P < 0.015). Positive expression for HIF-1 alpha was correlated with VEGF and PDGF-C expression in tumors (P < 0.001). There was a significant correlation between VEGF and PDGF-C expression in the cytoplasm of GBM tumor cells (P < 0.0001). We showed that VEGF expression in tumor cells was correlated with its expression in blood vessels (P < 0.0001). Endothelial cells with PDGF-C and VEGF positive expression were also positive for CD105 and their nuclei for Ki-67, confirming the neoangiogenic and proliferative influence of VEGF and PDGF-C. VEGF nuclear staining in tumor cells (P = 0.002) as well as nuclear staining for HIF-1 alpha and VEGF (P = 0.005) correlated with survival. In summary, our present findings of the concomitant upregulation of PDGF-C with VEGF in GBM tumor cells and vessels further reinforce the benefit of using combined anti-angiogenic approaches to potentially improve the therapeutic response for GBM.
conferenceObject A Lower Ki 67 Labelling Index (LI) Cut-Point Improves the Prognostic Assessment and Might Aid in the Diagnosis of Adult Adrenocortical Tumors(2018) MARTINS FILHO, Sebastiao N.; ALMEIDA, Madson Q.; SOARES, Ibere C.; WAKAMATSU, Alda; ALVES, Venancio; FRAGOSO, Maria C.; ZERBINI, Maria- Extracellular Matrix Proteome Remodeling in Human Glioblastoma and Medulloblastoma(2021) TROMBETTA-LIMA, Marina; ROSA-FERNANDES, Livia; ANGELI, Claudia B.; MORETTI, Isabele F.; FRANCO, Yollanda M.; MOUSESSIAN, Adaliana S.; WAKAMATSU, Alda; LERARIO, Antonio M.; OBA-SHINJO, Sueli M.; PASQUALUCCI, Carlos A.; MARIE, Suely K. N.; PALMISANO, GiuseppeMedulloblastomas (MBs) and glioblastomas (GBMs) are high-incidence central nervous system tumors. Different origin sites and changes in the tissue microenvironment have been associated with the onset and progression. Here, we describe differences between the extracellular matrix (ECM) signatures of these tumors. We compared the proteomic profiles of MB and GBM decellularized tumor samples between each other and their normal decellularized brain site counterparts. Our analysis revealed that 19, 28, and 11 ECM proteins were differentially expressed in MBs, GBMs, and in both MBs and GBMs, respectively. Next, we validated key findings by using a protein tissue array with 53 MB and 55 GBM cases and evaluated the clinical relevance of the identified differentially expressed proteins through their analysis on publicly available datasets, 763 MB samples from the GSE50161 and GSE85217 studies, and 115 GBM samples from RNAseq-TCGA. We report a shift toward a denser fibrillary ECM as well as a clear alteration in the glycoprotein signature, which influences the tumor pathophysiology.