EDWIN ROGER PARRA CUENTAS
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conferenceObject Combining Inhibitor of DNA - Binding Proteins and Angigenic Markers Expression Predict Long Term Survival of Patients with Non-Small Cell Lung Cancer(2013) ANTONANGELO, L.; TUMA, T. S.; VARGAS, F. S.; PARRA, E. R.; TERRA, R. M.; ACENCIO, M.; CAPELOZZI, V. L.Background: Inhibitor of DNA binding (Id) proteins is an emerging promise as biologic marker on oncogenic transformation, cancer progression and tumor angiogenesis, the last, by the regulation of vascular endothelial growth factor (VEGF) expression. Design: We evaluated Ids (1, 2 and 3), VEGF expression and microvessel density (CD34+) in tumor and stromal cells and their impact on survival of 85 patients with surgically excised lung squamous cell carcinoma and adenocarcinoma. Immunohistochemistry and morphometry were used for the quantitation and Kaplan-Meyer survival curves and Cox regression for the statistical analyses. Results: It was found that high Id-1 and VEGF expression and high microvessel density were associated with worse prognosis (Log Rank Test, p<0.001). The Cox model controlled for histological type, age, lymph node stage, Ids, VEGF and microvessel density demonstrated that age, lymph node stage, Id1 and Id3 expression and vascular density were significantly associated with overall survival. A point at the median for Id1, Id3 and vascular density divided patients into 2 groups of different prognosis. Those with higher expression of Id1, Id3 and vascular density had a higher risk of death than those with lower Id-1, Id-3 and microvessel density. Conclusions: Inhibitor of DNA binding (Id) proteins and vascular density are strongly related to prognosis, suggesting that treatment strategies aimed for preventing high Ids synthesis, or local responses to angiogenesis may have impact on NSLC survival.conferenceObject Combining Inhibitor of DNA - Binding Proteins and Angigenic Markers Expression Predict Long Term Survival of Patients with Non-Small Cell Lung Cancer(2013) ANTONANGELO, L.; TUMA, T. S.; VARGAS, F. S.; PARRA, E. R.; TERRA, R. M.; ACENCIO, M.; CAPELOZZI, V. L.Background: Inhibitor of DNA binding (Id) proteins is an emerging promise as biologic marker on oncogenic transformation, cancer progression and tumor angiogenesis, the last, by the regulation of vascular endothelial growth factor (VEGF) expression. Design: We evaluated Ids (1, 2 and 3), VEGF expression and microvessel density (CD34+) in tumor and stromal cells and their impact on survival of 85 patients with surgically excised lung squamous cell carcinoma and adenocarcinoma. Immunohistochemistry and morphometry were used for the quantitation and Kaplan-Meyer survival curves and Cox regression for the statistical analyses. Results: It was found that high Id-1 and VEGF expression and high microvessel density were associated with worse prognosis (Log Rank Test, p<0.001). The Cox model controlled for histological type, age, lymph node stage, Ids, VEGF and microvessel density demonstrated that age, lymph node stage, Id1 and Id3 expression and vascular density were significantly associated with overall survival. A point at the median for Id1, Id3 and vascular density divided patients into 2 groups of different prognosis. Those with higher expression of Id1, Id3 and vascular density had a higher risk of death than those with lower Id-1, Id-3 and microvessel density. Conclusions: Inhibitor of DNA binding (Id) proteins and vascular density are strongly related to prognosis, suggesting that treatment strategies aimed for preventing high Ids synthesis, or local responses to angiogenesis may have impact on NSLC survival.- Id-1, Id-2, and Id-3co-expression correlates with prognosis in stage I and II lung adenocarcinoma patients treated with surgery and adjuvant chemotherapy(2016) ANTONANGELO, Leila; TUMA, Taila; FABRO, Alexandre; ACENCIO, Milena; TERRA, Ricardo; PARRA, Edwin; VARGAS, Francisco; TAKAGAKI, Teresa; CAPELOZZI, VeraInhibitors of DNA binding/inhibitors of differentiation (Id) protein family have been shown to be involved in carcinogenesis. However, the roles of Id during lung adenocarcinoma (ADC) progression remain unclear. Eighty-eight ADC samples were evaluated for Id-1,2,3 level and angiogenesis (CD 34 and VEGF microvessel density) by immunohistochemistry and morphometry. The impact of these markers was tested on follow-up until death or recurrence. A significant difference between tumor and normal tissue was found for Id-1,2,3 expression (P < 0.01). In addition, high levels of nuclear Id-1 were associated with higher angiogenesis in the tumor stroma (P < 0.01). Equally significant was the association between patients in T1-stage and low cytoplasmic Id-2, as well as patients in stage-IIb and low Id-3. High cytoplasm Id-3 expression was also directly associated to lymph nodes metastasis (P = 0.05). Patients at stages I to III, with low Id-1 and Id-3 cytoplasm histoscores showed significant long metastasis-free survival time than those with high Id-1 or Id-3 expression (P = 0.04). Furthermore, high MVD-CD34 and MVD-VEGF expression were associated with short recurrence-free survival compared to low MVD-CD34 and MVD-VEGF expressions (P = 0.04). Cox model analyses controlled for age, lymph node metastasis, and adjuvant treatments showed that nuclear Id-1, cytoplasmic Id-3, and MVD-CD34 were significantly associated with survival time. Median score for nuclear Id-1 and cytoplasmic Id-3 divided patients in two groups, being that those with increased Id-1 and Id-3 presented higher risk of death. Ids showed an independent prognostic value in patients with lung ADC, regardless of disease stage. Id-1 and Id-3 should be considered new target candidates in the development of personalized therapy in lung ADC.
conferenceObject Multiplex Ligation Probe-dependent Amplification (MLPA) as an ancillary method for the diagnosis of malignant pleural effusion(2012) PARRA, E.; ROSOLEN, D.; KULIKOWSKI, L.; DUTRA, R.; CAPELOZZI, V. L.; VARGAS, F.; ACENCIO, M.; ANTONANGELO, L.Objective: A definitive diagnosis provided by the finding of malignant cells in pleural fluid (PF) can be established in around 50 % of patients with pleural malignancy. However, underdiagnosis risk in cytological suspicious cases is high, which makes the cytological diagnosis quite limited. This is an important clinical problem, especially if we consider that some patients, in bad clinical conditions, can not be submitted to a guided thoracoscopic biopsy. Method: Using multiplex ligation probe-dependent amplification (P315-MRC-Holland) we have studied sequence variations of EGFR gene and amplifications/deletions of chromosomal regions frequently associated to tumors (ATG4B, PAHs, PROS, NSD1, and CDGIF genes). Results: Forty-three malignant PF samples from patients with different cancers were evaluated, even in those cases with scarce pellet cells. Four benign pleural effusions were used as control. Gene sequence changes were observed in 13 (30.2 %) cases, while others copy number abnormalities were found in 19 (44.2 %). Conclusion: The findings suggest that MLPA could be considered an alternative tool to detect molecular genetic changes in malignant pleural effusions, since this technique is relatively low expensive and not time consuming. Our next challenge is to find the best combination of probes capable to recognize malignant cells of any origin in fresh samples of PF.conferenceObject Elastic-Collagen Profile in Emphysematous Airspaces from Different Chronic Fibrosing Lung Disorders(2013) MARCAL, L. J.; ANTONANGELO, L.; PARRA, E. R.; VARGAS, F. S.; TEODORO, W. R.; NASCIMENTO, E. C. T.; CAPELOZZI, V. L.Background: Parenchyma elastic and collagen components of chronic fibrosing lung disorders has been exhaustively investigated, but little attention has been aimed at the emphysematous airspaces present in bullous disease, smoking-related interstitial disease and usual interstitial pneumonia. The aim of this study was to evaluate whether elastic deposition accompanies collagen deposition in the repairing process of emphysematous airspaces in chronic fibrosing lung injuries. Design: The elastic and collagen fibers distribution were evaluated in emphysematous airspaces of bullous type I and II disease, smoking-related interstitial fibrosis and of usual interstitial pneumonia (UIP). Lung specimens obtained by surgical lung biopsy or by bullectomy divided the patients into four groups: 1) type I bullous disease (SPT-I; n=7); 2) type II bullous disease (SPT-II; n=12); 3) smoking-related interstitial pneumonia (SRIP; n=5) and 4) usual interstitial pneumonia/idiopathic pulmonary fibrosis (UIP/IPF; n=5). Collagen and elastic fibers were identified respectively by Picrosirius-polarization and Weigert's resorcin-fucsin staining and quantified by image analysis.The results were expressed in percentual area. Results: The proportion of collagen fibers was two times higher when compared with the elastic component in the four groups. In addition, a lower percentage of elastic and collagen fibers were observed in SRIP when compared with UIP/IPF, SPT-I and SPT-II. Conclusions: A smaller amount of elastic and collagen fibers accompanies the remodeling of the emphysematous airspaces in smoking-related interstitial pneumonia when compared to the other fibrosing diseases, suggesting a different remodeling spectrum in chronic fibrosing lung diseases.conferenceObject Overexpression of inhibitor of DNA-binding proteins and angiogenic markers have higher impact on survival of non small cell lung cancer patients(2012) SALES, Roberta; TUMA, Thayla; ACENCIO, Milena; TERRA, Ricardo; PARRA, Edwin; CAPELOZZI, Vera; ANTONANGELO, LeilaconferenceObject Elastic-Collagen Profile in Emphysematous Airspaces from Different Chronic Fibrosing Lung Disorders(2013) MARCAL, L. J.; ANTONANGELO, L.; PARRA, E. R.; VARGAS, F. S.; TEODORO, W. R.; NASCIMENTO, E. C. T.; CAPELOZZI, V. L.Background: Parenchyma elastic and collagen components of chronic fibrosing lung disorders has been exhaustively investigated, but little attention has been aimed at the emphysematous airspaces present in bullous disease, smoking-related interstitial disease and usual interstitial pneumonia. The aim of this study was to evaluate whether elastic deposition accompanies collagen deposition in the repairing process of emphysematous airspaces in chronic fibrosing lung injuries. Design: The elastic and collagen fibers distribution were evaluated in emphysematous airspaces of bullous type I and II disease, smoking-related interstitial fibrosis and of usual interstitial pneumonia (UIP). Lung specimens obtained by surgical lung biopsy or by bullectomy divided the patients into four groups: 1) type I bullous disease (SPT-I; n=7); 2) type II bullous disease (SPT-II; n=12); 3) smoking-related interstitial pneumonia (SRIP; n=5) and 4) usual interstitial pneumonia/idiopathic pulmonary fibrosis (UIP/IPF; n=5). Collagen and elastic fibers were identified respectively by Picrosirius-polarization and Weigert's resorcin-fucsin staining and quantified by image analysis.The results were expressed in percentual area. Descriptive ResultsStaining Disease Mean Std. Deviation Std. Error Minimum Maximum Picro-sirius STP-I 40.71 15.87 6.00 18.56 61.67 Picro-sirius STP-II 40.58 15.95 4.60 15.67 63.35 Picro-sirius SRIP 30.18 9.23 4.13 25.31 46.64 Picro-sirius UIP/IPF 40.99 13.99 6.26 24.76 60.07 Resorcina STP-I 19.97 10.63 4.02 3.71 33.76 Resorcina STP-II 18.42 6.17 1.78 10.19 26.70 Resorcina SRIP 11.86 9.72 4.35 1.87 25.62 Resorcina UIP/IPF 18.49 9.95 4.45 12.43 35.77 Results: The proportion of collagen fibers was two times higher when compared with the elastic component in the four groups. In addition, a lower percentage of elastic and collagen fibers were observed in SRIP when compared with UIP/IPF, SPT-I and SPT-II. Table 1. Conclusions: A smaller amount of elastic and collagen fibers accompanies the remodeling of the emphysematous airspaces in smoking-related interstitial pneumonia when compared to the other fibrosing diseases, suggesting a different remodeling spectrum in chronic fibrosing lung diseases.conferenceObject Epidermal growth factor receptor and related biomarkers evaluated by immunohistochemistry in patients with resected non-small cell lung cancer(2013) ANTONANGELO, Leila; SILVA, Bruna; TUMA, Thayla; MARCAL, Lia; ACENCIO, Milena; PARRA, Edwin; TERRA, Ricardo; VARGAS, Francisco; CAPELOZZI, VeraconferenceObject Pleural Fibroelastosis is a similar spectrum of Histopathology in Chronic Fibrosing Lung Disorders(2012) MARCAL, L.; PARRA, E. R.; ANTONANGELO, L.; CAPELOZZI, V.; VARGAS, F.; NASCIMENTO, E. C.; TEODORO, V.; SILVA, K. C.