NEILA APARECIDA DE SOUZA SILVA

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Instituto Central, Hospital das Clínicas, Faculdade de Medicina

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  • article 10 Citação(ões) na Scopus
    An integrative histopathologic clustering model based on immuno-matrix elements to predict the risk of death in malignant mesothelioma
    (2020) BALANCIN, Marcelo Luiz; TEODORO, Walcy Rosolia; FARHAT, Cecilia; MIRANDA, Tomas Jurandir de; ASSATO, Aline Kawassaki; SILVA, Neila Aparecida de Souza; VELOSA, Ana Paula; FALZONI, Roberto; AB'SABER, Alexandre Muxfeldt; RODEN, Anja C.; CAPELOZZI, Vera Luiza
    Objective Previous studies have reported a close relationship between malignant mesothelioma (MM) and the immune matricial microenvironment (IMM). One of the major problems in these studies is the lack of adequate adjustment for potential confounders. Therefore, the aim of this study was to identify and quantify risk factors such as IMM and various tumor characteristics and their association with the subtype of MM and survival. Methods We examined IMM and other tumor markers in tumor tissues from 82 patients with MM. These markers were evaluated by histochemistry, immunohistochemistry, immunofluorescence, and morphometry. Logistic regression analysis, cluster analysis, and Cox regression analysis were performed. Results Hierarchical cluster analysis revealed two clusters of MM that were independent of clinicopathologic features. The high-risk cluster included MM with high tumor cellularity, high type V collagen (Col V) fiber density, and low CD8(+) T lymphocyte density in the IMM. Our results showed that the risk of death was increased for patients with MM with high tumor cellularity (OR = 1.63, 95% CI = 1.29-2.89, P = .02), overexpression of Col V (OR = 2.60, 95% CI = 0.98-6.84, P = .04), and decreased CD8 T lymphocytes (OR = 1.001, 95% CI = 0.995-1.007, P = .008). The hazard ratio for the high-risk cluster was 2.19 (95% CI = 0.54-3.03, P < .01) for mortality from MM at 40 months. Conclusion Morphometric analysis of Col V, CD8(+) T lymphocytes, and tumor cellularity can be used to identify patients with high risk of death from MM.
  • conferenceObject
    Podocyte Injury in Membranous and Proliferative Lupus Nephritis: Distinct Underlying Mechanisms?
    (2012) REZENDE, Gabriela M.; VIANA, Vilma S. T.; MALHEIROS, Denise M.; LEON, Elaine P.; BORBA, Eduardo F.; SILVA, Neila A. S.; NORONHA, Irene L.; SILVA, Cleonice; BONFA, Eloisa
    Background/Purpose: Lupus nephritis (LN) is a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE) with proteinuria being the predominant common manifestation and may therefore reflect podocyte injury. Podocytes are highly specialized cells that have a relevant role in the glomerular filtration barrier and alteration in the expression of their biomarkers has been shown to be associated with podocyte dysfunction in some glomerulopathies. A systematic analysis of podocyte-associated molecules encom-passing different subcellular compartments was performed in a large series of LN biopsies. Expression of Wilms tumor protein (WT1), Synaptopodin (Synpo) and glomerular epithelial protein 1 (GLEPP1) with nuclear, cytoplasmic and membrane distribution respectively, were evaluated attempting to identify if podocyte phenotype is distinct in proliferative and membranous nephritis. Possible association of molecular expression alterations with long term proteinuria severity and outcome in lupus was also investigated. Methods: Immunohistochemistry analysis was performed using monoclonal antibodies to WT1, Synpo and GLEPP1 proteins in 52 biopsies from patients with lupus nephritis fulfilling the revised ACR criteria for SLE. Demographic, clinical and laboratorial data at the time of biopsy were analyzed. Results: Thirty-nine (75%) biopsies were classified as proliferative LN and thirteen (25%) as pure membranous class V. Immunohistochemistry analysis in normal kidney revealed preserved staining of WT1, Synpo and GLEPP1 podocyte biomarkers along the capillary walls. Preserved and concomitant WT1 and Synpo staining was observed in a significant higher frequency in pure class V biopsies than in proliferative LN (69.23 vs. 2.56%, p 0.0001). Likewise, preserved GLEPP1 expression was also more frequent in pure class V LN (53.85 vs. 2.86%, p 0.0002). Proteinuria and serum albumin levels at the time of biopsy did not statistically differ in the two groups (p 0.87 and p 0.41) whereas in the mean long-term follow-up of four years a tendency of lower proteinuria (p 0.050) was observed in those patients with biopsies expressing preserved WT1/Synpo staining. Conclusion: This is the first study comparing proliferative and membranous lupus nephritis which evaluated simultaneously the expression of proteins in different subcellular podocyte compartments and provided novel evidence of preserved podocyte structural architecture predominantly in membranous lesions which may account for a better long term outcome of patients with this LN histological class. These findings suggest possible different underlying mechanisms for proteinuria in both conditions.