VENANCIO AVANCINI FERREIRA ALVES
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, Faculdade de Medicina - Docente
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina - Líder
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina - Líder
17 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 17
- 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.
- 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.
- Distinctive molecular traits of hepatocellular carcinoma in patients with non-alcoholic steatohepatitis(2019) TORRECILLA, Sara; PINYOL, Roser; WANG, Huan; MONTIRONI, Carla; ANDREU-OLLER, Carmen; LEOW, Wei Qiang; MOEINI, Agrin; OLIVEIRA, Claudia; ALVES, Venancio Avancini Ferreira; LACHENMAYER, Anja; ROESSLER, Stephanie; MINGUEZ, Beatriz; SCHIRMACHER, Peter; BOFFETTA, Paolo; DUFOUR, Jean-Francois; THUNG, Swan N.; UZILOV, Andrew; CARRILHO, Flair Jose; CHANG, Charissa; SIA, Daniela; LLOVET, Josep M.
conferenceObject Clinicopathological Characteristics and Prognostic Value of HER2, PD-L1 and MSI Expression in Curative Resectable Gastric Cancer Patients(2019) PEREIRA, M. A.; RAMOS, M. F.; FARAJ, S. F.; DIAS, A. R.; CIRQUEIRA, C. D.; CHARRUF, A. Z.; PERROTTA, F. S.; MELLO, E. S.; ZILBERSTEIN, B.; CECCONELLO, I.; YAGI, O. K.; ALVES, V. A.; JUNIOR, U. R.- Expression Profile of Markers for Targeted Therapy in Gastric Cancer Patients: HER-2, Microsatellite Instability and PD-L1(2019) PEREIRA, Marina Alessandra; RAMOS, Marcus Fernando Kodama Pertille; DIAS, Andre Roncon; FARAJ, Sheila Friedrich; RIBEIRO, Renan Ribeiro e; CASTRIA, Tiago Biachi de; ZILBERSTEIN, Bruno; ALVES, Venancio Avancini Ferreira; JR, Ulysses Ribeiro; MELLO, Evandro Sobroza deBackground The assessment of human epidermal growth factor receptor 2 (HER2), microsatellite instability (MSI) and programmed cell death-ligand 1 (PD-L1) expression is relevant for the selection and effectiveness of targeted therapy in gastric cancer (GC). Objective We aimed to investigate the clinicopathological characteristics and prognosis of GC patients according to these profiles. Methods GC patients who underwent gastrectomy with D2 lymphadenectomy were eligible. HER2, MSI status and PD-L1 expression were analyzed by immunohistochemistry (IHC). Patients were grouped as follows: HER2+ group, immunotherapy (IT) group (MSI and/or PD-L1+), and non-targeted therapy (NTT) group (stable microsatellite and HER2/PD-L1-). Results Among 282 patients, 50 (17.7%) were HER2+ and 79 (28%) MSI/PD-L1+. Fifteen had HER2+ and MSI/PD-L1+, while 168 (59.6%) were in the NTT group. HER2+ GCs were related to male gender (p = 0.007), intestinal type (p = 0.001) and less advanced pTNM stage (p = 0.029). Older age (p = 0.003), subtotal gastrectomy (p = 0.025), intestinal type (p = 0.008), pN0 status (p = 0.002) and less advanced pTNM stage (p = 0.001) were associated with the IT group. IT GC had better disease-free survival (DFS) and overall survival than the NTT group (p = 0.015 and p = 0.027, respectively). Concerning patients eligible for the standard adjuvant therapy, the treatment impacted positively on DFS for HER2+ and NTT groups (p = 0.003 and p = 0.042, respectively). No difference in DFS was seen between IT patients who received perioperative/adjuvant therapy and those treated only with surgery (p = 0.160). Conclusions GC patients who exhibited markers that can serve as an indication for known targeted therapy represent 40.4% of cases. The IT group was associated with a better prognosis. No benefit with standard adjuvant treatment appears to be achieved in MSI/PD-L1+ GCs.
conferenceObject Hepatic epithelioid hemangioendotelioma: An international multicenter study(2019) ZAMPARELLI, Marco Sanduzzi; RIMOLA, Jordi; MONTIRONI, Carla; NUNES, Vinicius; ALVES, Venancio Avancini Ferreira; SAPENA, Victor; FORNER, Alejandro; CARRILHO, Flair Jose; DIAZ, Alba; FUSTER, Carla; FERRER, Joana; FUSTER, Josep; AYUSO, Carmen; SOLE, Manel; BRUIX, Jordi; REIG, Maria- Malignant Vascular Tumors of the Liver in Adults(2019) ALVES, Venancio Avancini Ferreira; RIMOLA, JordiHepatic angiosarcoma and epithelioid hemangioendothelioma (EHE) might be clinically considered a spectrum since, although more frequently presenting indolent behavior, EHE occasionally evolves to high-grade neoplasms. However, in most circumstances, pathological and immunohistochemical patterns define this differential diagnosis. More recently, molecular pathways for angiosarcoma and for EHE from other organs and from soft tissue have been proved different, paving the way for future morpho-molecular assessment of their hepatic counterpart. The frequency of liver involvement by Kaposi sarcoma in HIV-infected patients is lower nowadays. Histological findings and immunostaining for HHV-8 Ag are characteristic. Hepatic small vessel neoplasms have been recently recognized as important mimickers of angiosarcoma. The criteria for this differential diagnosis and the clinical behavior, up to now considered favorable, must be further studied.
conferenceObject COMPARISON OF TWO CUT-OFF VALUES OF THE FECAL IMMUNOCHEMICAL TEST DURING AN ORGANIZED COLORECTAL CANCER SCREENING(2019) SAFATLE-RIBEIRO, Adriana V.; SORBELLO, Mauricio P.; PFUETZENREITER, Vinicius; BASTOS, Victor R.; COHEN, Diane D.; SOUZA, Afonso H. Silva e; HASHIMOTO, Claudio L.; FRANCO, Joel L.; GOMES, Jackeline O.; ALVES, Venancio A.; CECCONELLO, Ivan; NAHAS, Sergio C.; ELUF NETO, Jose; RIBEIRO, Ulysses- Revised criteria for diagnosis of NIFTP reveals a better correlation with tumor biological behavior(2019) PANIZA, Ana Carolina de Jesus; MENDES, Thais Biude; VIANNA, Matheus Duarte Borges; THOMAZ, Debora Mota Dias; CHIAPPINI, Paula B. O.; COLAZZA-GAMA, Gabriel A.; LINDSEY, Susan Chow; CARVALHO, Marcos Brasilino de; ALVES, Venancio Avancini Ferreira; CURIONI, Otavio; BASTOS, Andre Uchimura; CERUTTI, Janete MariaThe recent reclassification of a follicular variant of papillary thyroid carcinoma (FVPTC), subset as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), aims to avoid overtreatment of patients with an indolent lesion. The diagnosis of NIFTP has recently been revisited using more rigid criteria. This study presents histological and molecular findings and a long clinical follow-up of 94 FVPTC, 40 cases of follicular adenoma (FTA) and 22 cases of follicular carcinoma (FTC) that were classified before the advent of the NIFTP reclassification. All slides were reviewed using these rigid criteria and analysis of numerous sections of paraffin blocks and reclassified as 7 NIFTPs, 2 EFVPTCs, 29 infiltrative FVPTC (IFVPTCs), 57 invasive EFVPTC (I-EFVPTCs), 39 FTAs and 22 FTCs. Remarkably, EFVPTC and NIFTP patients were all free of disease at the end of follow-up and showed no BRAF mutation. Only one NIFTP sample harbored mutations, an NRAS Q61R. PAX8/PPARG fusion was found in I-EFVPTCs and FTC. Although additional studies are needed to identify a specific molecular profile to aid in the diagnosis of lesions with borderline morphological characteristics, we confirmed that the BRAFV600E mutation is an important tool to exclude the diagnosis of NIFTP. We also show that rigorous histopathological criteria should be strongly followed to avoid missing lesions in which more aggressive behavior is present, mainly via the analysis of capsule or vascular invasion and the presence of papillary structures.
- Steatosis and steatohepatitis found in adults after death due to non-burn trauma(2019) REIS-JUNIOR, Paulo; TANIGAWA, Ryan; MESQUITA, Gustavo Heluani Antunes de; BASAN, Natalia; ALVES, Venancio; D'ALBUQUERQUE, Luiz Augusto Carneiro; ANDRAUS, WellingtonOBJECTIVE: With the increasing prevalence of steatosis, the number of steatotic liver grafts from deceased donors is also increasing. Thus, determining the prevalence and the population risk factors of steatosis may assist in risk stratification. The aim of this study was to evaluate the prevalence and predictors of steatosis and steatohepatitis among livers from adults who died due to non-burn trauma. METHODS: Specimens were collected from 224 adults undergoing autopsy at a regional autopsy referral center from September 2011 to April 2013. Histopathological examination was performed on six samples obtained from different lobes of each liver. The outcomes of interest were the presence of steatosis, steatohepatitis, NASH inflammation and NASH fibrosis. The main predictors were body mass index, abdominal circumference, liver weight and volume, presence of cholelithiasis, and siderosis. Our modeling strategy made use of a series of generalized linear models with a binomial family. RESULTS: Our sample had a mean age of 40 years; steatosis was diagnosed in 48.2% of cases, and steatohepatitis was diagnosed in 2.7%. The presence of a high proportion of fatty changes was more prevalent among males and older individuals, with the most affected age group being 41-60 years. When evaluating the crude odds ratio for steatosis, the factors significantly associated with an increased risk of steatosis were greater abdominal circumference, BMI, and liver weight and the presence of siderosis. CONCLUSION: Our study reinforces the role of older age, obesity and hepatomegaly as predictors of fatty liver disease. These variables should be considered in the assessment of fatty changes in the livers of potential liver donors.