TERESA YAE TAKAGAKI
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/09 - Laboratório de Pneumologia, Hospital das Clínicas, Faculdade de Medicina
LIM/09 - Laboratório de Pneumologia, Hospital das Clínicas, Faculdade de Medicina
3 resultados
Resultados de Busca
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- Usefulness of complementary next-generation sequencing and quantitative immunohistochemistry panels for predicting brain metastases and selecting treatment outcomes of non-small cell lung cancer(2019) MACHADO-RUGOLO, Juliana; FABRO, Alexandre Todorovic; ASCHERI, Daniel; FARHAT, Cecilia; AB'SABER, Alexandre Muxfeldt; SA, Vanessa Karen de; NAGAI, Maria Aparecida; TAKAGAKI, Teresa; TERRA, Ricardo; PARRA, Edwin Roger; CAPELOZZI, Vera LuizaTo demonstrate the usefulness of complementary next-generation sequencing (NGS) and immunohistochemistry (IHC) counting, we analyzed 196 patients with non-small cell lung cancer who underwent surgical resection and adjuvant chemotherapy. Formalin-fixed, paraffin-embedded samples of adenocarcinoma (ADC), squamous cell carcinoma, and large cell carcinoma were used to prepare tissue microarrays and were examined by protein H-score IHC image analysis and NGS for oncogenes and proto-oncogenes and genes of tumor suppressors, immune checkpoints, epithelial-mesenchymal transition factors, tyrosine kinase receptors, and vascular endothelial growth factors. In patients with brain metastases, primary tumors expressed lower PIK3CA protein levels. Overexpression of p53 and a higher PD-LI protein H-score were detected in patients who underwent surgical treatment followed by chemotherapy as compared with those who underwent only surgical treatment The absence of brain metastases was associated with wild-type sequences of genes EGFR, CD267, CTLA-4, and ZEBI. The combination of protein overexpression according to IHC and mutation according to NGS was rare (ie, represented by a very low percentage of concordant cases), except for p53 and vascular endothelial growth factor. Our data suggest that protein levels detected by IHC may be a useful complementary tool when mutations are not detected by NGS and also support the idea to expand this approach beyond ADC to include squamous cell carcinoma and even large cell carcinoma, particularly for patients with unusual clinical characteristics. Conversely, well-pronounced immunogenotypic features seemed to predict the clinical outcome after univariate and multivariate analyses. Patients with a solid ADC subtype and mutated genes EGFR, CTLA4, PDCDILG2, or ZEBI complemented with PD-L1 or p53 protein lower expression that only underwent surgical treatment who develop brain metastases may have the worst prognosis.
- Histomorphometric evaluation of the Ki-67 proliferation rate and CD34 microvascular and D2-40 lymphovascular densities drives the pulmonary typical carcinoid outcome(2018) VILHENA, Alyne Fonseca de; PEREIRA, Joao Carlos das Neves; PARRA, Edwin Roger; BALANCIN, Marcelo Luiz; AB'SABER, Alexandre; MARTINS, Vanessa; FARHAT, Cecilia; ABRANTES, Marcelo Militao; CAMPOS, Jose Ribas Milanez de; TEDDE, Miguel Lia; TAKAGAKI, Teresa; CAPELOZZI, Vera LuizaKi-67 has shown promise as a prognostic factor in pulmonary carcinoids. In this study, we sought to validate the importance of Ki-67 and study the relationships between Ki-67 and other stromal biomarkers of vascular density. We examined Ki-67, CD34, and D2-40 in tumor tissues from 128 patients with surgically excised typical carcinoid of the lung. We used immunohistochemistry and morphometry to evaluate the amount of tumor staining for cellular proliferation (Ki-67), microvascular density (CD34-MVD), and D2-40 lymphovascular density. The main outcome was overall survival, considered as life expectancy until death from metastasis. Specimens from patients with central tumors showed high CD34-MVD (P = .01), which was also significantly associated with a compromised surgical margin, lymph node metastasis, and clinical stage Ib. Equally significant was high D2-40 lymphovascular density in central specimens with a compromised surgical margin and lymph node metastasis. A high Ki-67 proliferation rate was significantly associated with tumors from patients with clinical stage IIb, IIIa, and IV disease. Multivariate Cox model analysis demonstrated that tumor location and stage, surgical margin, tumor size, and N stage were significantly related to survival time (P < .05). Quantitative staining of the tumor for Ki-67 and CD34-MVD served as prognostic factors (P < .05), which were more relevant than the surgical and pathological stage. Ki-67 greater than 5% and CD34-MVD greater than 7% staining comprise a subset of patients with higher death hazard; this outcome may harbor evidence for further prospective studies of target therapy after surgical resection.
- Hyaluronidase splice variants are associated with histology and outcome in adenocarcinoma and squamous cell carcinoma of the lung(2012) SA, Vanessa Karen de; OLIVIERI, Eloisa; PARRA, Edwin Roger; AB'SABER, Alexandre Muxfeldt; TAKAGAKI, Teresa; SOARES, Fernando Augusto; CARRARO, Dirce; CARVALHO, Lina; CAPELOZZI, Vera LuizaHeterogeneity of hyaluronidase (HYAL) expression has been identified in tumors and shows promise as an indicator of disease progression. The expression profile of alternatively spliced forms of HYAL was evaluated in tumors and normal lung tissue from 69 resected tumors of patients with adenocarcinomas and squamous cell carcinomas. HYAL1-wild-type (wt) and variants 1 to 5, HYAL2-wt, and HYAL3-wt, and variants 1 to 3 were identified by polymerase chain reaction and direct sequencing. Different proportions of the 3 HYAL-wt and variants were expressed in tumor and normal lung tissues. HYAL1-wt was associated with a poorer prognosis and HYAL3-vl with a better prognosis. HYAL splice variants are associated with histology and outcome, suggesting that strategies aimed at modulating their levels may be effective for lung cancer treatment.