Submitted by PPG Medicina e Ci?ncias da Sa?de (medicina-pg@pucrs.br) on 2018-10-24T17:02:58Z No. of bitstreams: 1 JULIANA_LORENZONI_ALTHOFF.pdf: 23099056 bytes, checksum: 2ebbb4db3683a55ddc1d12778cf36c64 (MD5) / Approved for entry into archive by Sheila Dias (sheila.dias@pucrs.br) on 2018-10-25T14:52:43Z (GMT) No. of bitstreams: 1 JULIANA_LORENZONI_ALTHOFF.pdf: 23099056 bytes, checksum: 2ebbb4db3683a55ddc1d12778cf36c64 (MD5) / Made available in DSpace on 2018-10-25T15:03:03Z (GMT). No. of bitstreams: 1 JULIANA_LORENZONI_ALTHOFF.pdf: 23099056 bytes, checksum: 2ebbb4db3683a55ddc1d12778cf36c64 (MD5) Previous issue date: 2009-03-23 / Background: The colon-rectal cancer is the third most frequent neoplasia in the western world with the highest mortality rates. The progression of normal colon tissue to invasiveness neoplasia is follow by several processes called carcinogenesis. Afterwards it converges to the cellular migration and metastasis of the tissue. The metabolic ways of the E26 (Ets) transcription factors, identified in a great variety of species, contributes in this process, by activating or repressing the DNA transcription. Specially, the prostate-derived Ets factor (PDEF) which prognosis and cancer colon-rectal relation action is not completely elucidating at the moment. Methods: A retrospective cohort of patients with pathologic stage I ? III colon-rectal cancer, diagnosed and treated in the same institution between 2002 and 2008, was study. Histological and clinical features as well as clinical outcomes and survival were reviewed. The tissue microarrays (TMA), immunohistochemical analysis and image capture quantification were carried out in representative blocks of tumor with antibodies for the detection of the PDEF expression and Ki-67. The endpoints were to determine the prevalence of the PDEF protein expression and its correlation with these population?s prognostic factors. Results: The sample was constituted 46 patients and the median follow-up was 23,2 months. There was a trend towards loss of PDEF protein expression according to the patients? clinical stage. PDEF expression values were 30,3%, 25,8% and 14,7% in stages I, II and III, respectively. There was not a significant correlation with the lost of PDEF protein expression and the clinical and pathological characteristics along with the proportion of Ki-67 proliferative marker and the patient?s global survival. Conclusions: These results suggest that the PDEF protein, member of the Ets family, act as a repression gene of cancer colon-rectal carcinogenesis. The PDEF expression analysis can be an interesting prognostic marker and a therapeutic target. New studies with more patients and a long follow-up are necessary to validate these results. / Base te?rica: O c?ncer colorretal ? a terceira neoplasia mais freq?ente no mundo ocidental com taxas de mortalidade ainda consideras altas. A progress?o do tecido epitelial do c?lon normal at? o est?gio de neoplasia invasiva ? acompanhada de uma s?rie de processos celulares chamados carcinog?nese que, ao fim, convergem para o potencial de migra??o celular e metastatiza??o. As vias metab?licas da fam?lia dos genes Ets (E26 - sequ?ncia espec?fica de transcri??o), identificada em uma grande diversidade de esp?cies, contribuem neste processo, ativando ou reprimindo transcri??es de DNA. Em especial o fator derivado prost?tico (PDEF) cujo progn?stico e mecanismo de a??o relacionado ao c?ncer colorretal, at? o momento, n?o est? claramente elucidado. M?todos: Uma coorte retrospectiva de pacientes com carcinoma colorretal est?gios de I a III, diagnosticados e tratados na mesma institui??o de 2002 a 2008, foi estudada. As caracter?sticas histol?gicas e cl?nicas, bem como os dados de evolu??o e a sobrevida foram revisados. A an?lise de imunoistoqu?mica com m?todo de matriz de amostras teciduais (TMA) e a quantifica??o por captura de imagem foram realizadas em blocos representativos do tumor com anticorpos para detec??o da express?o da prote?na PDEF e Ki-67. Os objetivos eram detectar a preval?ncia da express?o da prote?na PDEF e sua correla??o com fatores progn?sticos nesta popula??o. Resultados: A amostra foi constitu?da de 46 pacientes e tempo de seguimento mediano de 23,2 meses. Houve tend?ncia a perda da prote?na PDEF conforme o estadiamento dos pacientes sendo a express?o de 30,3%, 25,8% e 14,7% nos est?gio I, II e III, respectivamente, P=0,416. N?o encontrou-se associa??o significativa entre os achados cl?nico-patol?gicos, a dosagem do marcador de prolifera??o celular Ki-67 e a sobrevida global dos pacientes com a perda da express?o da prote?na PDEF. Conclus?es: Os resultados sugerem que a prote?na PDEF, membro da fam?lia Ets, atue como gene repressor da carcinog?nese do c?ncer colorretal. A an?lise de sua express?o pode se tornar um interessante marcador progn?stico e alvo terap?utico. S?o necess?rios novos estudos com amostras maiores e tempo de seguimento mais longo a fim de validar estes achados.