EVANDRO SOBROZA DE MELLO

(Fonte: Lattes)
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Lattes
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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

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Revista / Livro: Journal of Surgical Oncology ×

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  • article 30 Citação(ões) na Scopus
    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, Paulo
    BackgroundHistomorphological 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.
  • article 1 Citação(ões) na Scopus
    Gastric cancer with microsatellite instability displays increased thymidylate synthase expression
    (2022) PEREIRA, Marina A.; DIAS, Andre R.; RAMOS, Marcus F. K. P.; CARDILI, Leonardo; MORAES, Rafael D. R.; ZILBERSTEIN, Bruno; NAHAS, Sergio C.; MELLO, Evandro S.; JR, Ulysses Ribeiro
    Background Gastric cancer (GC) with microsatellite instability (MSI) is a less aggressive disease and associated with resistance to 5-fluorouracil (5-FU)-based chemotherapy (CMT). Thymidylate synthase (TS) is inhibited by 5-FU, and another potential mediator of therapeutic resistance to 5-FU. Therefore, we aimed to analyze the association between MSI and TS expression in GC, and its impact on disease outcomes. Methods We retrospectively evaluated GC who underwent D2-gastrectomy. MSI and TS were analyzed by immunohistochemistry. We also investigated p53 expression, PD-L1 status, and tumor-infiltrating lymphocytes (CD4 and CD8). Results Out of 284 GC, 60 (21.1%) were MSI. Median TS-score for all cases was 16.5. TS expression was significantly higher in MSI compared to microsatellite-stable (MSS; p < 0.001). Considering both status, GC were classified in four groups: 167 (58.8%) MSS + TS-low; 57 (20.1%) MSS + TS-High; 24 (8.5%) MSI + TS-low; and 36 (12.7%) MSI + TS-high. MSI + TS-high group had less advanced pTNM stage, higher CD8+T cells levels (p < 0.001) and PD-L1 positivity (p < 0.001). Normal p53 expression was related to MSI GC (p < 0.001). Improved survival was observed in MSI + TS-high, but no survival benefit was seen with CMT. Conclusion MSI GC was associated with high TS levels, which may explain therapeutic resistance to 5-FU. Additionally, MSI + TS-high showed better survival, but without improvement with CMT.
  • article 6 Citação(ões) na Scopus
    Cytotoxic T-lymphocyte-associated protein 4 in gastric cancer: Prognosis and association with PD-L1 expression
    (2021) PEREIRA, Marina Alessandra; CASTRIA, Tiago Biachi de; RAMOS, Marcus Fernando Kodama Pertille; DIAS, Andre Roncon; CARDILI, Leonardo; MORAES, Rafael Dyer Rodrigues; ZILBERSTEIN, Bruno; NAHAS, Sergio Carlos; JR, Ulysses Ribeiro; MELLO, Evandro Sobroza de
    Background Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is one of the most studied immune checkpoint in gastric cancer (GC). However, the prognostic role of CTLA-4 expression in GC is poorly described. This study aimed to evaluate CTLA-4 expression in GC and its impact on survival, including patients treated with standard platinum-based chemotherapy (CMT), and association with PD-L1 expression. Methods All GC patients who underwent D2-gastrectomy were investigated retrospectively. Tumor samples were examined for CTLA-4 and PD-L1 by immunohistochemistry. Tumor-infiltrating inflammatory cells, including CD4 + and CD8 + , were also examined. Results Among the 284 GC patients included, 159 (56%) were CTLA-4 positive and the remaining 125 (44%) were classified as negative. CTLA-4 positive GC was associated with increased inflammatory cell infiltration (p < 0.001), high CD8 + T cells (p = 0.016) and PD-L1 expression (p = 0.026). Considering GC referred for treatment, CTLA-4 negative patients who received CMT had a significant improvement in disease-free survival compared to untreated CLTA-4 negative (p = 0.028). In multivariate analysis, GC positive for both CTLA-4 and PD-L1 had a prognostic impact on survival. Conclusion CTLA-4 positive was associated with PD-L1 expression and a high tumor-infiltrating CD8 + T cells. Accordingly, positivity for both CTLA-4 and PD-L1 was an independent factor associated to better survival in GC patients.
  • article 54 Citação(ões) na Scopus
    Clinicopathological and prognostic features of Epstein-Barr virus infection, microsatellite instability, and PD-L1 expression in gastric cancer
    (2018) PEREIRA, Marina A.; RAMOS, Marcus F. K. P.; FARAJ, Sheila F.; DIAS, Andre R.; YAGI, Osmar K.; ZILBERSTEIN, Bruno; CECCONELLO, Ivan; ALVES, Venancio A. F.; MELLO, Evandro S. de; RIBEIRO JR., Ulysses
    Background and ObjectivesGastric cancer (GC) has recently been categorized in molecular subtypes, which include Epstein-Barr (EBV)-positive and microsatellite instability (MSI) tumors. This distinction may provide prognostic information and identifies therapeutic targets. The aim of this study was to evaluate EBV, MSI, and PD-L1 immunoexpression in GC and its relationship with clinicopathological characteristics and patient's prognosis. MethodsWe evaluated 287 GC patients who underwent D2-gastrectomy through immunohistochemistry for DNA mismatch repair proteins and PD-L1, and in situ hybridization for EBV detection utilizing tissue microarray. ResultsEBV-positive and MSI were identified in 10.5% and 27% of the GCs, respectively. EBV positivity was associated to male gender (P=0.032), proximal location (P<0.001), undetermined Lauren type (P<0.001), poorly differentiated histology (P=0.043) and severe inflammatory infiltrate (P<0.001). MSI-tumors were associated to older age (P=0.002), subtotal gastrectomy (P=0.004), pN0 (P=0.024) and earlier TNM stage (P=0.020). PD-L1-positive was seen in 8.8% of cases, with predominant expression in EBV-positive GC (P<0.001). MSI was associated to better survival outcomes. ConclusionEBV-positive GCs had increased PD-L1 expression, while MSI GC had better survival outcome. EBV and MSI subgroups are distinct GC entities, their recognition is feasible by conventional techniques, and it may help individualize follow-up and guide adjuvant therapy.
  • article 2 Citação(ões) na Scopus
    Reply to ""Poorly differentiated clusters in colorectal liver metastases: Prognostic significance in synchronous and metachronous metastases""
    (2018) FONSECA, Gilton M.; MELLO, Evandro S. de; COELHO, Fabricio F.; KRUGER, Jaime A. P.; FARAJ, Sheila F.; JEISMANN, Vagner B.; PAWLIK, Timothy M.; HERMAN, Paulo
  • article 24 Citação(ões) na Scopus
    Gastric cancer molecular classification and adjuvant therapy: Is there a different benefit according to the subtype?
    (2020) RAMOS, Marcus F. K. P.; PEREIRA, Marina A.; AMORIM, Larissa C.; MELLO, Evandro S. de; FARAJ, Sheila F.; JR, Ulysses Ribeiro; HOFF, Paulo M. G.; CECCONELLO, Ivan; CASTRIA, Tiago B. de
    Background Gastric cancer (GC) has been defined in distinct molecular subtypes with different therapeutic implications. However, its clinical significance and prognosis regarding standard chemotherapy (CMT) remains unclear. This study aimed to analyze the impact of perioperative or adjuvant treatment among subtypes of GC. Methods We retrospectively evaluated all stage II/III patients with GC who underwent a curative gastrectomy. Based on immunohistochemistry and in situ hybridization techniques, GC was classified into five subtypes: Epstein-Barr virus (EBV) positive, microsatellite instability (MSI), e-cadherin aberrant, p53-aberrant, and p53-normal. Results Among the 178 CG included, 111 patients received CMT and 67 were treated with surgery alone. Survival analysis showed that p53-aberrant GC treated with CMT had better disease-free survival (DFS) compared with surgery alone (P = .001).There was no significant difference in DFS between patients who received CMT and those with surgery alone for EBV, MSI, E-cadherin, and p53-normal GC. An improvement in overall survival was observed only for E-cadherin (P = .001) and p53-aberrant (P < .001) patients who received CMT. Conclusions CMT showed different impact on the survival of CG according to the molecular subtype. No survival benefit was observed for EBV and MSI groups who received CMT. GC with p53-aberrant had a significant benefit in survival with standard therapy.
  • article 24 Citação(ões) na Scopus
    Lymph node regression after neoadjuvant chemotherapy: A predictor of survival in gastric cancer
    (2020) PEREIRA, Marina Alessandra; RAMOS, Marcus Fernando Kodama Pertille; DIAS, Andre Roncon; CARDILI, Leonardo; RIBEIRO, Renan Ribeiro e; CHARRUF, Amir Zeide; CASTRIA, Tiago Biachi de; ZILBERSTEIN, Bruno; CECONELLO, Ivan; ALVES, Venancio Avancini Ferreira; RIBEIRO JR., Ulysses; MELLO, Evandro Sobroza de
    Background and Objective Neoadjuvant chemotherapy (nCMT) has been increasingly used in advanced gastric cancer (GC). However, the prognostic impact of tumor response remains unclear. This study aimed to evaluate if tumor response at the primary site and lymph nodes (LN) correlate with survival in GC patients after nCMT. Methods Patients with gastric adenocarcinoma treated with nCMT followed by gastrectomy were evaluated. Residual tumor was graded from 0% to 100%, defining two groups: poor (PR) and major response (MR). LN regression rate (LNRR) was determined based on tumor/fibrosis examination at each LN and a cutoff value established by receiver operating characteristic curve. Results Among 62 cases, 20 (32.2%) had MR and 42 (67.7%) PR. Smaller size, diffuse histology, lower ypT status and less advanced stage were associated with the MR group. Based on cutoff value of 57, 45.6% and 54.4% patients were classified as low-LNRR and high-LNRR. High-LNRR correlated with absence of venous, lymphatic and perineural invasion, and less advanced stage. Survival was equivalent between MR and PR (P = .956). High-LNRR had better disease-free survival (DFS) than low-LNRR (P < .001). In multivariate analysis, only LNRR associated with DFS. Conclusion High-LNRR associates with DFS in GC treated with nCMT. Response at the primary site does not correlate with survival.