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
6 resultados
Resultados de Busca
Agora exibindo 1 - 6 de 6
- 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.
- 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.
- Dissecting and Reconstructing Matrix in Malignant Mesothelioma Through Histocell-Histochemistry Gradients for Clinical Applications(2022) BALANCIN, Marcelo Luiz; BALDAVIRA, Camila Machado; PRIETO, Tabatha Gutierrez; MACHADO-RUGOLO, Juliana; FARHAT, Cecilia; ASSATO, Aline Kawassaki; VELOSA, Ana Paula Pereira; TEODORO, Walcy Rosolia; AB'SABER, Alexandre Muxfeldt; TAKAGAKI, Teresa Yae; CAPELOZZI, Vera LuizaBackgroundMalignant pleural mesotheliomas (MM) are known for their heterogenous histology and clinical behavior. MM histology reveals three major tumor cell populations: epithelioid, sarcomatoid, and biphasic. Using a dissecting approach, we showed that histochemical gradients help us better understand tumor heterogeneity and reconsider its histologic classifications. We also showed that this method to characterize MM tumor cell populations provides a better understanding of the underlying mechanisms for invasion and disease progression. MethodsIn a cohort of 87 patients with surgically excised MM, we used hematoxylin and eosin to characterize tumor cell populations and Movat's pentachrome staining to dissect the ECM matrisome. Next, we developed a computerized semi-assisted protocol to quantify and reconstruct the ECM in 3D and examined the clinical association between the matricellular factors and patient outcome. ResultsEpithelioid cells had a higher matrix composition of elastin and fibrin, whereas, in the sarcomatoid type, hyaluronic acid and total collagen were most prevalent. The 3D reconstruction exposed the collagen I and III that form channels surrounding the neoplastic cell blocks. The estimated volume of the two collagen fractions was 14% of the total volume, consistent with the median estimated area of total collagen (12.05 mm(2)) for epithelioid MM. ConclusionDifferential patterns in matricellular phenotypes in MM could be used in translational studies to improve patient outcome. More importantly, our data raise the possibility that cancer cells can use the matrisome for disease expansion and could be effectively targeted by anti-collagen, anti-elastin, and/or anti-hyaluronic acid therapies.
- Identification of Predictors of Metastatic Potential in Paragangliomas to Develop a Prognostic Score (PSPGL)(2024) IGUCHI, Daniela Yone Veiga; FILHO, Sebastiao Nunes Martins; SOARES, Ibere Cauduro; SIQUEIRA, Sheila Aparecida Coelho; ALVES, Venancio Avancini Ferreira; ASSATO, Aline Kawassaki; YANG, Ji Hoon; ALMEIDA, Madson Q.; FRAGOSO, Maria Candida Barisson Villares; FAGUNDES, Gustavo Freitas Cardoso; MENDONCA, Berenice B.; JR, Delmar Muniz Lourenco; HOFF, Ana O.; CASTRONEVES, Luciana Audi; FERRAZ-DE-SOUZA, Bruno; GIANNELLA, Maria Lucia Cardillo Correa; PEREIRA, Maria Adelaide AlbergariaContext Paragangliomas (PGLs) are rare tumors in adrenal and extra-adrenal locations. Metastasis are found in approximately 5% to 35% of PGLs, and there are no reliable predictors of metastatic disease.Objective This work aimed to develop a prognostic score of metastatic potential in PGLs.Methods A retrospective analysis was conducted of clinical data from a cohort with PGLs and tumor histological assessment. Patients were divided into metastatic PGL (presence of metastasis) and nonmetastatic PGL (absence of metastasis >= 96 months of follow-up) groups. Univariate and multivariable analysis were performed to identify predictors of metastatic potential. A prognostic score was developed based on coefficients of multivariable analysis. Kaplan-Meier curves were generated to estimate disease-specific survival (DSS).Results Out of 263 patients, 35 patients had metastatic PGL and 110 patients had nonmetastatic PGL. In multivariable analysis, 4 features were independently related to metastatic disease and composed the Prognostic Score of Paragangliomas (PSPGL): presence of central or confluent necrosis (33 points), more than 3 mitosis/10 high-power field (HPF) (28 points), extension into adipose tissue (20 points), and extra-adrenal location (19 points). A PSPGL of 24 or greater showed similar sensitivity with higher specificity than the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and Grading System for Adrenal Pheochromocytoma and Paraganglioma (GAPP). PSPGL less than or equal to 20 was associated with a risk of metastasis of approximately 10%, whereas a PSPGL of 40 or greater was associated with approximately 80%. The presence of metastasis and Ki-67 of 3% or greater were related to lower DSS.Conclusion The PSPGL, composed of 4 easy-to-assess parameters, demonstrated good performance in predicting metastatic potential and good ability in estimating metastasis risk.