ALINE KAWASSAKI ASSATO
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina
12 resultados
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- 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.
- Comprehensive analysis of immune, extracellular matrices and pathogens profile in lung granulomatosis of unexplained etiology(2018) SOUZA, Paola da Costa; DONDO, Patricia Suemi; SOUZA, Gabriela; LOPES, Deborah; MOSCARDI, Marcel; MARTINHO, Vinicius de Miranda; LOURENCO, Rodolfo Daniel de Mattos; PRIETO, Tabatha; BALANCIN, Marcelo Luiz; ASSATO, Aline Kawassaki; TEODORO, Walcy Rosolia; RODRIGUES, Silvia; LIMA, Mariana; CASTELLANO, Maria Vera; COLETTA, Ester; PARRA, Edwin Roger; CAPELOZZI, Vera LuizaThis study analyzed the type 1 and type 2 T helper (Th1/Th2) cytokines (including interleukins), immune cellular, matrix profile, and pathogens in granulomas with unexplained etiology compared to those with infectious and noninfectious etiology. Surgical lung biopsies from 108 patients were retrospectively reviewed. Histochemistry, immunohistochemistry, immunofluorescence, morphometry and polymerase chain reaction were used, respectively, to evaluate total collagen and elastin fibers, collagen I and III, immune cells, cytokines, matrix metalloproteinase-9, myofibroblasts, and multiple usual and unusual pathogens. No relevant polymerase chain reaction expression was found in unexplained granulomas. A significant difference was found between the absolute number of eosinophils, macrophages, and lymphocytes within granulomas compared to uninvolved lung tissue. Granulomas with unexplained etiology (UEG) presented increased number of eosinophils and high expression of interleukins (ILs) IL-4/IL-5 and transforming growth factor-beta. In sarcoidosis, CD4/CD8 cell number was significantly higher within and outside granulomas, respectively; the opposite was detected in hypersensitivity pneumonitis. Again, a significant difference was found between the high number of myofibroblasts and matrix metalloproteinase-9 in UEG, hypersensitivity pneumonitis, and sarcoidosis compared to granulomas of tuberculosis. Granulomas of paracoccidioisis exhibited increased type I collagen and elastic fibers. Th1 immune cellular profile was similar among granulomas with unexplained, infectious, and noninfectious etiology. In contrast, modulation of Th2 and matrix remodeling was associated with more fibroelastogenesis and scarring of lung tissue in UEG compared to infectious and noninfectious. We concluded that IL-4/IL-5 and transforming growth factor-beta might be used as surrogate markers of early fibrosis, reducing the need for genotyping, and promise therapeutic target in unexplained granulomas.
- Combining Immunoprofile, Immunogenic Collagen and Mismatch Repair Proteins Predicts Risk of Death and Target Therapy in Malignant Mesothelioma(2019) MACHADO-RUGOLO, J.; BALANCIN, M.; MARTINS, V.; MIRANDA, J.; ASSATO, A.; SOUZA, N.; VELOSA, A. P.; FALZONI, R.; AB'SABER, A.; TEODORO, W.; CAPELOZZI, V.
conferenceObject Immune-profilling depends on immunogenic collagen and mismatch proteins to predict death and therapy in malignant mesothelioma(2019) MORGANTETTI, G.; BALANCIN, M.; MARTINS, V.; MIRANDA, J. T. De; ASSATO, A. K.; SOUZA, N. A. de; VELOSA, A. P. Pereira; TEODORO, W. Rosolia; MEDEIROS, G. A. de; FALZONI, R.; AB'SABER, A. M.; CAPELOZZI, V.conferenceObject Expanding the TMA Method to Investigate Phylogenetic Relationships Between Primary and Metastatic Hepatocellular Carcinoma(2018) MARTINS FILHO, Sebastiao N.; WAKAMATSU, Alda; VILLACORTA-MARTIN, Carlos; ASSATO, Aline K.; CRAIG, Amanda; CARRILHO, Flair; THUNG, Swan; VILLANUEVA, Augusto; ALVES, VenancioconferenceObject Expanding the TMA Method to Investigate Phylogenetic Relationships Between Primary and Metastatic Hepatocellular Carcinoma(2018) MARTINS FILHO, Sebastiao N.; WAKAMATSU, Alda; VILLACORTA-MARTIN, Carlos; ASSATO, Aline K.; CRAIG, Amanda; CARRILHO, Flair; THUNG, Swan; VILLANUEVA, Augusto; ALVES, Venancio- 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 LuizaObjective 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.
- In Situ Overexpression of Matricellular Mechanical Proteins Demands Functional Immune Signature and Mitigates Non-Small Cell Lung Cancer Progression(2021) YAEGASHI, Lygia Bertalha; BALDAVIRA, Camila Machado; PRIETO, Tabatha Gutierrez; MACHADO-RUGOLO, Juliana; VELOSA, Ana Paula Pereira; SILVEIRA, Lizandre Keren Ramos da; ASSATO, Aline; AB'SABER, Alexandre Muxfeldt; FALZONI, Roberto; TAKAGAKI, Teresa; SILVA, Pedro Leme; TEODORO, Walcy Rosolia; CAPELOZZI, Vera LuizaNon-small cell lung carcinoma (NSCLC) is a complex cancer biome composed of malignant cells embedded in a sophisticated tumor microenvironment (TME) combined with different initiating cell types, including immune cells and cancer-associated fibroblasts (CAFs), and extracellular matrix (ECM) proteins. However, little is known about these tumors' immune-matricellular relationship as functional and mechanical barriers. This study investigated 120 patients with NSCLC to describe the immune-matricellular phenotypes of their TME and their relationship with malignant cells. Immunohistochemistry (IHC) was performed to characterize immune checkpoints (PD-L1, LAG-3, CTLA-4+, VISTA 1), T cells (CD3+), cytotoxic T cells (CD8(+), Granzyme B), macrophages (CD68+), regulatory T cells (FOXP3+, CD4+), natural killer cells (CD57+), and B lymphocytes (CD20+), whereas CAFs and collagen types I, III, and V were characterized by immunofluorescence (IF). We observed two distinct functional immune-cellular barriers-the first of which showed proximity between malignant cells and cytotoxic T cells, and the second of which showed distant proximity between non-cohesive nests of malignant cells and regulatory T cells. We also identified three tumor-associated matricellular barriers: the first, with a localized increase in CAFs and a low deposition of Col V, the second with increased CAFs, Col III and Col I fibers, and the third with a high amount of Col fibers and CAFs bundled and aligned perpendicularly to the tumor border. The Cox regression analysis was designed in two steps. First, we investigated the relationship between the immune-matricellular components and tumor pathological stage (I, II, and IIIA), and better survival rates were seen in patients whose tumors expressed collagen type III > 24.89 fibers/mm(2). Then, we included patients who had progressed to pathological stage IV and found an association between poor survival and tumor VISTA 1 expression > 52.86 cells/mm(2) and CD3+ <= 278.5 cells/mm(2). We thus concluded that differential patterns in the distribution of immune-matricellular phenotypes in the TME of NSCLC patients could be used in translational studies to predict new treatment strategies and improve patient outcome. These data raise the possibility that proteins with mechanical barrier function in NSCLC may be used by cancer cells to protect them from immune cell infiltration and immune-mediated destruction, which can otherwise be targeted effectively with immunotherapy or collagen therapy.
- Combined use of immunohistochemical markers of basal and luminal subtypes in urothelial carcinoma of the bladder: Association with clinicopathological features and outcomes(2021) RAVANINI, Juliana Naves; ASSATO, Aline Kawassaki; WAKAMATSU, Alda; ALVES, Venancio Avancini FerreiraOBJECTIVES: Whole genome expression profiles allow the stratification of bladder urothelial carcinoma into basal and luminal subtypes which differ in histological patterns and clinical behavior. Morpho-molecular studies have resulted in the discovery of immunohistochemical markers that might enable discrimination between these two major phenotypes of urothelial carcinoma. METHODS: We used two combinations of immunohistochemical markers, i.e., cytokeratin (CK) 5 with CK20 and CK5 with GATA3, to distinguish subtypes, and investigated their association with clinicopathological features, presence of histological variants, and outcomes. Upon searching for tumor heterogeneity, we compared the findings of primary tumors with their matched lymph node metastases. We collected data from 183 patients who underwent cystectomy for high-grade muscle-invasive urothelial carcinoma, and representative areas from the tumors and from 76 lymph node metastasis were organized in tissue microarrays. RESULTS: Basal immunohistochemical subtype (CK5 positive and CK20 negative, or CK5 positive and GATA3 negative) was associated with the squamous variant. The luminal immunohistochemical subtype (CK5 negative and CK20 positive, or CK5 negative and GATA3 positive) was associated with micropapillary and plasmacytoid variants. Remarkably, only moderate agreement was found between the immunohistochemical subtypes identified in bladder tumors and their lymph node metastasis. No significant difference in survival was observed when using either combination of the markers. CONCLUSION: This study demonstrates that these three routinely used immunohistochemical markers could be used to stratify urothelial carcinomas of the bladder into basal and luminal subtypes, which are associated with several differences in clinicopathological features.