ADHEMAR LONGATTO FILHO
Projetos de Pesquisa
Unidades Organizacionais
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina
8 resultados
Resultados de Busca
Agora exibindo 1 - 8 de 8
- Phospho-mTOR in non-tumour and tumour bladder urothelium: Pattern of expression and impact on urothelial bladder cancer patients(2014) AFONSO, Julieta; LONGATTO-FILHO, Adhemar; SILVA, Vitor Moreira Da; AMARO, Teresina; SANTOS, Iucio L.Urothelial bladder carcinoma (UBC) is heterogeneous in its pathology and clinical behaviour. Evaluation of prognostic and predictive biomarkers is necessary, in order to produce personalised treatment options. The present study used immunohistochemistry to evaluate UBC sections containing tumour and non-tumour areas from 76 patients, for the detection of p-mTOR, CD31 and D2-40 (blood and lymphatic vessels identification, respectively). Of the non-tumour and tumour sections, 36 and 20% were scored positive for p-mTOR expression, respectively. Immunoexpression was observed in umbrella cells from non-tumour urothelium, in all cell layers from non-muscle-invasive (NMI) tumours (including expression in superficial cells), and in spots of cells from muscle-invasive (MI) tumours. Positive expression decreased from non-tumour to tumour urothelium, and from pTl/pTis to pT3/pT4 tumours; however, the few pT3/pT4 positive cases had worse survival rates, with 5-year disease-free survival being significantly lower. Angiogenesis occurrence was impaired in pT3/pT4 tumours that did not express p-mTOR. In conclusion, p-mTOR expression in non-tumour umbrella cells is likely a reflection of their metabolic plasticity, and extension to the inner layers of the urothelium in NMI tumours is consistent with an enhanced malignant potential. The expression in cell spots in a few MI tumours and absence of expression in the remaining tumours is intriguing and requires further research. Additional studies regarding the up- and downstream effectors of the mTOR pathway should be conducted.
- Characterization of PAR1 and FGFR1 expression in invasive breast carcinomas: Prognostic significance(2012) TIBURCIO, Marta; COSTA, Sandra M. A.; DUARTE, Maria De Fatima; SCHMITT, Fernando C.; LONGATTO FILHO, AdhemarBreast cancer is the most common cause of cancer mortality among women worldwide. Among the several factors associated with breast cancer development, angiogenesis plays an essential role and has currently emerged as a potential diagnostic, prognostic and therapeutic target. Protease-activated receptor 1 (PAR1) and fibroblast growth factor receptor 1 (FGFR1) have important activities in tumor angiogenesis and progression. The aim of this study was to investigate the prognostic significance of these two receptors, hypothesising significant correlations between receptor expression in tumor angiogenesis and clinicopathological parameters customarily used in breast cancer prognosis and prediction. Formalin-fixed and paraffin-embedded samples of ductal invasive breast carcinomas were used to analyze the expression of PAR1 and FGFR1, in the tumor cells as well as in the tumor stroma, and further determine intratumoral microvessel density (iMVD) to quantify intratumoral angiogenesis. Correlations between PAR1 and FGFR1 expression in tumor cells and stroma, iMVD and several clinicopathological parameters and molecular markers used in breast cancer diagnosis have been addressed. The correlation between PAR1 and FGFR1 suggests an association of the two receptors with a more aggressive breast cancer phenotype and, consequently, a potential role during tumor progression. The results reported in the present study also emphasize the importance of microenvironmental factors in tumor progression, while precluding the positive association between iMVD and breast cancer aggressiveness.
- Characterization of topoisomerase II alpha and minichromosome maintenance protein 2 expression in anal carcinoma(2017) SCAPULATEMPO-NETO, Cristovam; VEO, Carlos; FREGNANI, Jose Humberto T. G.; LORENZI, Adriana; MAFRA, Allini; MELANI, Armando G. F.; LOAIZA, Edgar Antonio Aleman; ROSA, Luciana Albina Reis; OLIVEIRA, Cristina Mendes De; LEVI, Jose Eduardo; LONGATTO-FILHO, AdhemarThe present study aimed to ascertain the significance of topoisomerase II alpha (TOP2A) and minichromosome maintenance protein (MCM) 2 expression in anal carcinoma. A total of 75 anal lesions were retrieved from the files of the Department of Pathology of Barretos Cancer Hospital (Barretos, Brazil) in order to verify the human papillomavirus (HPV) statuses of these lesions and characterize the immunohistochemical expression levels of TOP2A and MCM2 in anal carcinoma, as these are important markers for cervical HPV-induced lesions; their expression was also compared with respect to p16 and Ki-67. The vast majority of the cases tested positive for HPV16 (84%); 1 case tested positive for both HPV16 and HPV18. Positive HPV16 status was more frequent in early stages than in advanced stages (P=0.008). Positive immunohistochemical reactivity for MCM2 and TOP2A protein was observed in 71.6 and 100% of cases, respectively. Positive reactivity for p16 was significantly associated (P=0.001) with histological grade, and was more commonly expressed in squamous cell carcinoma than adenocarcinomas. HPV16 was strongly associated with positive p16 protein expression (76.6%). However, the high expression of Ki-67 combined with the high expression of p16 was predominantly observed in Stage III-IV cases. MCM2, TOP2A, p16 and Ki-67 exhibited intense positive staining in the anal lesions, indicating that these markers were significantly and constantly expressed in anal carcinoma.
- Detection of the Epstein-Barr virus in blood and bone marrow mononuclear cells of patients with aggressive B-cell non-Hodgkin's lymphoma is not associated with prognosis(2012) MARQUES, Herlander; CATARINO, Raquel; DOMINGUES, Nelson; BARROS, Eliane; PORTELA, Catarina; ALMEIDA, Maria Ines; COSTA, Sandra; REIS, Rui Manuel; MEDEIROS, Rui; LONGATTO-FILHO, AdhemarThe Epstein-Barr virus (EBV) is associated with a large spectrum of lymphoproliferative diseases. Traditional methods of EBV detection include the immunohistochemical identification of viral proteins and DNA probes to the viral genome in tumoral tissue. The present study explored the detection of the EBV genome, using the BALF5 gene, in the bone marrow or blood mononuclear cells of patients with diffuse large B-cell lymphomas (DLBCL) and related its presence to the clinical variables and risk factors. The results show that EBV detection in 21.5% of patients is not associated with age, gender, staging, B symptoms, international prognostic index scores or any analytical parameters, including lactate dehydrogenase (LDH) or beta-2 microglobulin (B2M). The majority of patients were treated with R-CHOP-like (rituximab. cyclophosphamide, doxorubicin, vincristine and prednisolone or an equivalent combination) and some with CHOP-like chemotherapy. Response rates [complete response (CR) + partial response (PR)] were not significantly different between EBV-negative and -positive cases, with 93.2 and 88.9%, respectively. The survival rate was also similar in the two groups, with 5-year overall survival (OS) rates of 64.3 and 76.7%, respectively. However, when analyzing the treatment groups separately there was a trend in EBV-positive patients for a worse prognosis in patients treated with CHOP-like regimens that was not identified in patients treated with R-CHOP-like regimens. We conclude that EBV detection in the bone marrow and blood mononuclear cells of DLBC patients has the same frequency of EBV detection on tumoral lymphoma tissue but is not associated with the risk factors, response rate and survival in patients treated mainly with immunochemotherapy plus rituximab. These results also suggest that the addition of rituximab to chemotherapy improves the prognosis associated with EBV detection in DLBCL.
- Centrosome amplification in chondrosarcomas: A primary cell culture and cryopreserved tumor sample study(2017) PINHEIRO, Carla Aparecida; SOARES, Ibere Cauduro; PENNA, Valter; SQUIRE, Jeremy; REIS, Rui Manuel Vieira; SILVA, Sandra Regina Morini da; CARVALHO, Isabela de; CAMPAROTO, Marjori Leiva; SILVA, Maicon Fernando Zanon da; LONGATTO FILHO, AdhemarThe genetics background underlying the aggressiveness of chondrosarcoma (CS) is poorly understood. One possible cause of malignant transformation is chromosomal instability, which involves an error in mitotic segregation due to numerical and/or functional abnormalities of centrosomes. The present study aimed to evaluate centrosome amplification in cryopreserved samples of tumor tissue from patients with CS. An analysis was performed on 3 primary cultures of tumors from patients who underwent surgery between January 2012 and December 2012 at the Department of Orthopedics at the Barretos Cancer Hospital (Barretos, Brazil). Additionally, cryopreserved tumor specimens were analyzed from 10 patients. The data were assessed using immunocytochemistry and immunohistochemistry staining techniques with monoclonal antibody anti-gamma-tubulin. A total of 4 samples of CS cultured cells were obtained from 3 patients. A recurrence of a histological grade III tumor was detected in a female patient with Ollier's syndrome. The other 2 cases were grade I and III. The incidence of centrosome amplification in the primary cultures ranged from 15-64% of the cells. Whereas control cultured fibroblasts showed baseline levels of 4% amplified cells. For the cryopreserved specimens, two independent observers analyzed each sample and counted the cells stained with.-tubulin, verifying the percentage of affected cells to be a mean of 14%, with the number of clusters ranging between 0-6 per slide. In conclusion, centrosome amplification was found to be a consistent biological feature of CS and may underlie chromosomal instability in this tumor.
- Ki-67 and CD100 immunohistochemical expression is associated with local recurrence and poor prognosis in soft tissue sarcomas, respectively(2013) CAMPOS, Marcelo; CAMPOS, Silvana Gisele Pegorin De; RIBEIRO, Guilherme Gomes; EGUCHI, Flavia Coltri; SILVA, Sandra Regina Morini Da; OLIVEIRA, Cleyton Zanardo De; COSTA, Allini Mafra Da; CURCELLI, Emilio Carlos; NUNES, Marcos Ceita; PENNA, Valter; LONGATTO-FILHO, AdhemarSoft tissue sarcomas (STSs) are a heterogeneous group of mesenchymal tumors of >50 subtypes. However, STSs represent <1% of types of cancer. Despite this low frequency, the disease is aggressive and treatment, when possible, is based on traditional chemotherapies. A number of cases of resistance to adjuvant therapies have been reported. Metastases are commonly identified in STS patients during diagnosis and the development of effective clinical parameters is crucial for correct management of the disease. The use of biological Markers in cancer is a useful tool to determine patient prognosis. Ki-67 is a protein marker for proliferation of somatic cells and is widely used in prognostic studies of various types of tumor, including STSs. Cluster of differentiation 100 (CD100) is a member of the semaphorin family. The family was initially described as axon guidance molecules important for angiogenesis, organogenesis, apoptosis and neoplasia. CD100 was previously utilized as a prognostic factor in tumors and also in STSs. In the present study, protein expression of Ki-67 and CD100 was analyzed by immunohistochemistry in samples of STS patients of the Barretos Cancer Hospital (Barretos, Brazil) to establish prognostic criteria of the disease. Results demonstrate a correlation between CD100 expression and poor prognosis, consistent with a previous study. Moreover, the expression of Ki-67 was identified to correlate with presence of local or locoregional recurrence. To the best of our knowledge, no large casuistic study has revealed this correlation between Ki-67 and local recurrence in STSs. The use of Ki-67 and CD100 as markers in clinical pathological analysis may be suitable as a prognostic criterion in disease progression.
- Characterization of p16 and E6 HPV-related proteins in uterine cervix high-grade lesions of patients treated by conization with large loop excision(2013) RONCAGLIA, Maria Teresa; FREGNANI, Jose Humberto T. G.; TACLA, Maricy; CAMPOS, Silvana Gisele Pegorin De; CAIAFFA, Helio Hehl; AB'SABER, Alexandre; MOTA, Eduardo Vieira Da; ALVES, Venancio Avancini Ferreira; BARACAT, Edmund C.; LONGATTO FILHO, AdhemarCervical cancer and its precursor lesions 'represent a significant public health problem for developing and less-developed countries. Cervical carcinogenesis is strongly correlated with persistent high-risk human papillomavirus (HPV) infection, which is mostly associated with expression of the p16 and E6 HPV-related proteins. The aim of this present study was to determine the expression of the p16 and E6 proteins in females with high-grade lesions treated with conization, and to discuss the role of these proteins as prognostic markers following treatment. In total, 114 females were treated for high-grade cervical intraepithelial neoplasia (CIN, grades 2/3) by conization with large loop excision of the transformation zone (LLETZ). Following surgery, the patients returned within 30-45 days for post-operative evaluation. A follow-up was conducted every 6 months for 2 years. At each follow-up appointment, a Pap smear, colposcopy and HPV DNA test were performed. E6 and p16 immunohistochemical tests were conducted on the surgical specimens. The positive expression of p16 was correlated with the presence of lesions with increased severity in the surgical specimens (P=0.0001). The expression of E6 did not demonstrate the same correlation (P=0.131). The HPV DNA hybrid, collected in the first post-operative consultation as a predictor of the cytological abnormalities identified at the 24-month follow-up assessment, presented a sensitivity of 55.6%, a specificity of 84.8%, a positive predictive value of 33.3% and a negative predictive value of 93.3%. The role of p16INK4A as a marker of CIN was also demonstrated; the expression of p16 and E6, however, did not appear to be of any prognostic value in predicting the clearance of high-risk HPV following conization. A negative hybrid capture test was correlated with a disease-free outcome.
- Retrospective analysis of breast cancer prognosis among young and older women in a Brazilian cohort of 738 patients, 1985-2002(2016) VAZQUEZ, Fabiana De Lima; SILVA, Thiago Buosi; VIEIRA, Rene Alonisio Da Costa; COSTA, Allini Mafra Da; SCAPULATEMPO, Cristovam; FREGNANI, Jose Humberto Tavares Guerreiro; MAUAD, Edmundo Carvalho; LONGATTO, Adhemar; SYRJANEN, Kari JuhaniInvasive breast cancer (BC) is infrequent among women aged.5.40 years, however, the disease outlook in these younger patients is generally worse than among older women. The present study aimed to compare socio-demographic, clinical and pathological characteristics, and their association with long-term survival, between two random cohorts of young (<= 40 years) and older (50-69 years) Brazilian patients with BC. The cohort comprised of 738 randomly selected women who were diagnosed with BC at Barretos Cancer Hospital, Pio XII Foundation (Barretos, Brazil) between January 1985 and December 2002; the patients included young women (n=376) and older women (n=362). The current analysis suggested that BC in young women is associated with numerous pathological features of aggressiveness. Second cancer and bilateral BC were independent predictors of a poor outcome in the younger group. Furthermore, C-erB-2 was positively correlated with poor outcome in the older group, whereas estrogen receptor status and TNM stage were associated with disease prognosis in both groups. The overall survival rates of the two age groups were similar except when analyzed according the treatment period (1997-2002). Although patients aged <= 40 years harbored tumors with more aggressive clinicopathological characteristics, these characteristics were not independent predictors of overall survival. The present study indicates that medical advances associated with prevention of breast cancer may improve screening programs, which may therefore increase early diagnosis and subsequently lower mortality rates.