title: The destruction complex of beta-catenin in colorectal carcinoma and colonic adenoma.
abstract: OBJECTIVE
  To evaluate the destruction complex of beta-catenin by the expression of the proteins beta-catetenin, adenomatous polyposis coli, GSK3β, axin and ubiquitin in colorectal carcinoma and colonic adenoma.
  
  
  METHODS
  Tissue samples from 64 patients with colorectal carcinoma and 53 patients with colonic adenoma were analyzed. Tissue microarray blocks and slides were prepared and subjected to immunohistochemistry with polyclonal antibodies in carcinoma, adjacent non-neoplastic mucosa, and adenoma tissues. The immunoreactivity was evaluated by the percentage of positive stained cells and by the intensity assessed through of the stained grade of proteins in the cytoplasm and nucleus of cells. In the statistical analysis, the Spearman correlation coefficient, Student's t, χ2, Mann-Whitney, and McNemar tests, and univariate logistic regression analysis were used.
  
  
  RESULTS
  In colorectal carcinoma, the expressions of beta-catenin and adenomatous polyposis coli proteins were significantly higher than in colonic adenomas (p<0.001 and p<0.0001, respectively). The immunoreactivity of GSK3β, axin 1 and ubiquitin proteins was significantly higher (p=0.03, p=0.039 and p=0.03, respectively) in colorectal carcinoma than in the colonic adenoma and adjacent non-neoplastic mucosa. The immunohistochemistry staining of these proteins did not show significant differences with the clinical and pathological characteristics of colorectal cancer and colonic adenoma.
  
  
  CONCLUSIONS
  These results suggest that, in adenomas, the lower expression of the beta-catenin, axin 1 and GSK3β proteins indicated that the destruction complex of beta-catenin was maintained, while in colorectal carcinoma, the increased expression of beta-catenin, GSK3β, axin 1, and ubiquitin proteins indicated that the destruction complex of beta-catenin was disrupted.
  
  
  OBJECTIVE
  Avaliar o complexo de destruição da betacatenina no carcinoma colorretal e no adenoma do colo pela expressão das proteínas betacatenina, adenomatous polyposis coli, GSK3β, axina e ubiquitina.
  Amostras de tecidos de 64 doentes com carcinoma colorretal e de 53 pacientes com adenoma do colo foram analisadas. Blocos de tecidos foram submetidos ao estudo imuno-histoquímico com anticorpos policlonais nos tecidos do carcinoma, mucosa não neoplásica adjacente e adenoma. A imunorreatividade foi avaliada pela porcentagem de positividade de células coradas e pela intensidade do grau de coloração das proteínas no citoplasma e no núcleo das células. Na análise estatística, foram utilizados o coeficiente de correlação de Spearman, os testes t de Student, χ2, Mann-Whitney e de McNemar, e a análise de regressão logística univariada.
  
  
  RESULTS
  No carcinoma colorretal, as expressões da betacatenina e da adenomatous polyposis coli foram significativamente maiores do que em adenomas do colo (p<0,001 e p<0,0001, respectivamente). A imunorreatividade das proteínas GSK3β, axina 1 e ubiquitina foi significativamente maior (p=0,03, p=0,039 e p=0,03, respectivamente) no carcinoma colorretal do que no adenoma e na mucosa não neoplásica adjacente. A coloração imuno-histoquímica dessas proteínas não apresentou diferenças significantes em relação às características clinicopatológicas do câncer colorretal e do adenoma.
  Em adenomas, as menores expressões de betacatenina, axina 1 e GSK3β indicaram que o complexo de destruição da betacatenina estava conservado, enquanto que, no carcinoma colorretal, o aumento das expressões da betacatenina, GSK3β, 1 axina, e ubiquitina indicaram que o complexo de destruição de betacatenina estava alterado.
authors.affiliation: Hospital do Servidor Público Estadual "Francisco Morato de Oliveira", São Paulo, SP, Brazil.
authors.forename: Guilherme Muniz
authors.initials: GM
authors.lastname: Bourroul
authors.affiliation: Hospital do Servidor Público Estadual "Francisco Morato de Oliveira", São Paulo, SP, Brazil.
authors.forename: Hélio José
authors.initials: HJ
authors.lastname: Fragoso
authors.affiliation: Hospital do Servidor Público Estadual "Francisco Morato de Oliveira", São Paulo, SP, Brazil.
authors.forename: José Walter Feitosa
authors.initials: JW
authors.lastname: Gomes
authors.affiliation: Hospital do Servidor Público Estadual "Francisco Morato de Oliveira", São Paulo, SP, Brazil.
authors.forename: Vivian Sati Oba
authors.initials: VS
authors.lastname: Bourroul
authors.affiliation: Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Celina Tizuko Fujiyama
authors.initials: CT
authors.lastname: Oshima
authors.affiliation: Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Thiago Simão
authors.initials: TS
authors.lastname: Gomes
authors.affiliation: Faculdade de Medicina do ABC, Santo André, SP, Brazil.
authors.forename: Gabriela Tognini
authors.initials: GT
authors.lastname: Saba
authors.affiliation: Hospital do Servidor Público Estadual "Francisco Morato de Oliveira", São Paulo, SP, Brazil.
authors.forename: Rogério Tadeu
authors.initials: RT
authors.lastname: Palma
authors.affiliation: Hospital do Servidor Público Estadual "Francisco Morato de Oliveira", São Paulo, SP, Brazil.
authors.forename: Jaques
authors.initials: J
authors.lastname: Waisberg
mesh_terms: D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D011125:Adenomatous Polyposis Coli / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D060466:Axin Protein / Q000378:metabolism; D060465:Axin Signaling Complex / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D012004:Rectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D012189:Retrospective Studies; D025801:Ubiquitin / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: C555451:AXIN1 protein, human; D060466:Axin Protein; D060465:Axin Signaling Complex; D009363:Neoplasm Proteins; D025801:Ubiquitin; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta