EVANDRO SOBROZA DE MELLO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, Faculdade de Medicina - Docente
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
35 resultados
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- Tumor thickness as a predictive factor of lymph node metastasis and disease recurrence in T1N0 and T2N0 squamous cell carcinoma of the oral tongue(2014) MATOS, Leandro Luongo de; MANFRO, Gabriel; SANTOS, Ricardo Vieira dos; STABENOW, Elaine; MELLO, Evandro Sobroza de; ALVES, Venancio Avancini F.; PINTO, Fabio Roberto; KULCSAR, Marco Aurelio Vamondes; BRANDAO, Lenine Garcia; CERNEA, Claudio RobertoObjective. The aim of the study was to compare the thickness of primary tumors with the frequency of nodal metastases and survival in patients surgically treated for T1/T2N0 oral tongue squamous cell carcinoma. Study Design. This is a retrospective longitudinal study with 74 patients. Results. None of the patients with a tumor thickness (TT) <= 7 mm presented with nodal metastasis, whereas 25 of the patients with a TT > 7 mm (51.0%) developed metastases (P < .0001). Multivariate analysis showed that TT > 7 mm was a risk factor for occult nodal metastasis (odds ratio = 8.7; P = .002) with 81.9% accuracy. TT > 10 mm was also a predictive factor of worse disease-free survival in these patients (hazard ratio = 12.2; P = .003). Conclusions. Tumor thickness of greater than 7 mm is predictive of a higher incidence of lymph node metastasis, and a TT > 10 mm is predictive of worse disease-free survival in squamous cell carcinoma of the oral tongue.
- Prognostic significance of poorly differentiated clusters and tumor budding in colorectal liver metastases(2018) FONSECA, Gilton M.; MELLO, Evandro S. de; FARAJ, Sheila F.; KRUGER, Jaime A. P.; COELHO, Fabricio F.; JEISMANN, Vagner B.; LUPINACCI, Renato M.; CECCONELLO, Ivan; ALVES, Venancio A. F.; PAWLIK, Timothy M.; HERMAN, PauloBackgroundHistomorphological features have been described as prognostic factors after resection of colorectal liver metastases (CLM). The objectives of this study were to assess the prognostic significance of tumor budding (TB) and poorly differentiated clusters (PDC) among CLM, and their association with other prognostic factors. MethodsWe evaluated 229 patients who underwent a first resection of CLM. Slides stained by HE were assessed for TB, PDC, tumor border pattern, peritumoral pseudocapsule, peritumoral, and intratumoral inflammatory infiltrate. Lymphatic and portal invasion were evaluated through D2-40 and CD34 antibody. ResultsFactors independently associated with poor overall survival were nodules>4 (P=0.002), presence of PDC G3 (P=0.007), portal invasion (P=0.005), and absence of tumor pseudocapsule (P=0.006). Factors independently associated with disease-free survival included number of nodules>4 (P<0.001), presence of PDC G3 (P=0.005), infiltrative border (P=0.031), portal invasion (P=0.006), and absent/mild peritumoral inflammatory infiltrate (P=0.002). PDC and TB were also associated with histological factors, as portal invasion (TB), peritumoral inflammatory infiltration (PDC), infiltrative border, and absence of tumor pseudocapsule (TB and PDC). ConclusionsThis is the first study demonstrating PDC as a prognostic factor in CLM. TB was also a prognostic factor, but it was not an independent predictor of survival.
- 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.
- Hepatic granulomas: Differential diagnosis(2018) MELLO, E. S. de; ALVES, V. A. Ferreira
- External validation of the AJCC Cancer Staging Manual, 8th edition, in an independent cohort of oral cancer patients(2017) MATOS, Leandro Luongo; DEDIVITIS, Rogerio Aparecido; KULCSAR, Marco Aurelio Vamondes; MELLO, Evandro Sobroza de; ALVES, Venancio Avancini F.; CERNEA, Claudio RobertoObjectives: To evaluate the new American Joint Committee on Cancer (AJCC) cancer staging manual (8th edition) in an independent cohort of patients surgically treated for oral squamous cell carcinoma in order to determine whether the upstaging of pT and pN classification was indicative of a worse prognosis. Methods: A cohort of 298 patients was analyzed retrospectively. Results: Of these patients, 22.8% received an upstaging when the depth of invasion was included into the pT classification. Similarly, 29.2% of them were upstaged when extracapsular extension was added to pN classification. Twenty-eight of 68 patients (41.2%) that received an upstaging of pT classification died, and 23 (33.8%) experienced disease recurrence compared to 98/229 (42.8%) and 68/229 (29.7%), respectively, for those with the same pT during follow-up. With regard to pN classification, 70.6% of upstaged patients (60/85) died, and 50.6% (43/85) developed recurrence of the disease compared to 63/205 (30.7%) and 42/205 (20.5%), respectively, for those with the same pN during follow-up. Patients who were upstaged in pT classification presented a worse DFS (51.1% versus 80.4%, P = 0.007) and OS (31.5% versus 58.6%, P = 0.017). Similarly, those that were upstaged in pN classification presented a worse DFS (17.1% versus 61.2%, P = 0.001) and OS (8.5% versus 37.9%, P < 0.001). Conclusion: The new AJCC cancer staging manual (8th edition) allows a better stratification of oral SCC patients. By including the depth of invasion to the pT classification and extranodal extension to the pN classification, a worse disease-free and overall survival was assessed for these patients.
bookPart Noções básicas de patologia e imunoistoquímica(2013) ALVES, Venâncio Avancini Ferreira; MELLO, Evandro Sobroza de; LONGATO FILHO, Adhemar- Prognostic implications of tumor-infiltrating lymphocytes in association with programmed cell death ligand 1 expression in remnant gastric cancer(2022) PEREIRA, Marina Alessandra; RAMOS, Marcus Fernando Kodama Pertille; DIAS, Andre Roncon; CARDILI, Leonardo; MORAES, Rafael Dyer Rodrigues de; RIBEIRO, Renan Ribeiro E.; ALVES, Venancio Avancini Ferreira; ZILBERSTEIN, Bruno; MELLO, Evandro Sobroza de; JR, Ulysses RibeiroObjective: Remnant gastric cancer (RGC) is usually associated with a worse prognosis. As they are less common and very heterogeneous tumors, new prognostic and reliable determinants are required to predict patients' clinical course for RGC. This study aimed to investigate the tumor-infiltrating lymphocytes (TILs) and programmed cell death ligand 1 (PD-L1) status as prognostic biomarkers in a cohort of patients with RGC to develop an immune -related score.Methods: Patients with gastric cancer (GC) who underwent curative intent gastrectomy were retrospectively investigated. RGC resections with histological diagnosis of gastric adenocarcinoma were enrolled in the study. The risk score based on immune parameters was developed using binary logistic regression analysis. RGCs were divided into high-risk (HR), intermediate-risk (IR), and low-risk (LR) groups based on their immune score. The markers (CD3+, CD4+/CD8+ T cells and PD-L1) were selected for their potential prognostic, therapeutic value, and evaluated by immunohistochemistry (IHC).Results: A total of 42 patients with RGC were enrolled in the study. The score based on immune parameters exhibited an accuracy of 79% [the area under the receiver operating characteristic curve (AUC)=0.79, 95% confidence interval (95% CI), 0.63-0.94, P=0.002], and the population was divided into 3 prognostic groups: 10 (23.8%) patients were classified as LR, 15 (35.7%) as IR, and 17 (40.5%) as HR groups. There were no differences in clinicopathological and surgical characteristics between the three groups. In survival analysis, HR and IR groups had worse disease-free survival and overall survival rates compared to the LR group. In the multivariate analysis, lymph node metastasis and the immune score risk groups were independent factors related to worse survival.Conclusions: A scoring system with immune-related markers was able to distinguish prognostic groups of RGC associated with survival. Accordingly, tumor-infiltrating immune lymphocytes and PD-L1 status may serve as a potential prognostic biomarker for patients with RGC.
- Quantification of C4d deposition and hepatitis C virus RNA in tissue in cases of graft rejection and hepatitis C recurrence after liver transplantation(2015) SONG, Alice Tung Wan; MELLO, Evandro Sobroza de; ALVES, Venancio Avancini Ferreira; CAVALHEIRO, Norma de Paula; MELO, Carlos Eduardo; BONAZZI, Patricia Rodrigues; TENGAN, Fatima Mitiko; FREIRE, Maristela Pinheiro; BARONE, Antonio Alci; D'ALBUQUERQUE, Luiz Augusto Carneiro; ABDALA, EdsonHistology is the gold standard for diagnosing acute rejection and hepatitis C recurrence after liver transplantation. However, differential diagnosis between the two can be difficult. We evaluated the role of C4d staining and quantification of hepatitis C virus (HCV) RNA levels in liver tissue. This was a retrospective study of 98 liver biopsy samples divided into four groups by histological diagnosis: acute rejection in patients undergoing liver transplant for hepatitis C (RejHCV+), HCV recurrence in patients undergoing liver transplant for hepatitis C (HCVTx+), acute rejection in patients undergoing liver transplant for reasons other than hepatitis C and chronic hepatitis C not transplanted (HCVTx-). All samples were submitted for immunohistochemical staining for C4d and HCV RNA quantification. Immunoexpression of C4d was observed in the portal vessels and was highest in the HCVTx- group. There was no difference in C4d expression between the RejHCV+ and HCVTx+ groups. However, tissue HCV RNA levels were higher in the HCVTx+ group samples than in the RejHCV+ group samples. Additionally, there was a significant correlation between tissue and serum levels of HCV RNA. The quantification of HCV RNA in liver tissue might prove to be an efficient diagnostic test for the recurrence of HCV infection.
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.- Immunohistochemical expression of thymidylate synthase and prognosis in gastric cancer patients submitted to fluoropyrimidine-based chemotherapy(2018) PEREIRA, Marina Alessandra; RAMOS, Marcus Fernando Kodama Pertille; DIAS, Andre Roncon; FARAJ, Sheila Friedrich; CIRQUEIRA, Cinthya dos Santos; MELLO, Evandro Sobroza de; ZILBERSTEIN, Bruno; ALVES, Venancio Avancini Ferreira; RIBEIRO JR., UlyssesObjective: Adjuvant chemotherapy with 5-fluorouracil (5-FU) has been widely used in gastric cancer (GC) patients to prevent relapse after curative resection. 5-FU acts by inhibiting thymidylate synthase (TS), and high levels of TS correlate with resistance to treatment with fluoropyrimidines. The aim of this study was to evaluate the expression of TS in GC patients, and its relation with clinicopathological characteristics and prognosis in adjuvant chemotherapy with 5-FU. Methods: We retrospectively evaluated 285 patients who underwent D2-gastrectomy with curative intent. TS expression was determined by immunohistochemistry (IHC) in tumor cells by tissue microarray (TMA). TS level was evaluated according to the intensity and percentage of cells marked by a score system. Patients were divided in three groups according to their TS-score: negative, low and high. Results: TS expression was positive in 92.3% of GC. TS-high, TS-low and TS-negative were observed in 46.3%, 46.0% and 7.7% of patients, respectively. High-TS GC were associated with older age (P=0.007), high neutrophil/lymphocyte ratio (P=0.048), well/moderately differentiated histology (P=0.001), intestinal Lauren type (P<0.001) and absence of perineural invasion (P=0.003). Among 285 patients, 133 stage II/III patients (46.7%) received chemotherapy with 5-FU. In survival analysis, TS-high was associated with worse disease-free survival (DFS) in stage III GC patients who received 5-FU-based chemotherapy (P=0.007). Multivariate analysis revealed that total gastrectomy, poorly differentiated tumors and high TS-score were associated with worse DFS in stage III GC patients. Conclusions: High TS-score in stage III GC was associated with poor DFS in patients treated with fluoropyrimidine-based chemotherapy.