title: beta-Catenin and p53 analyses of a breast carcinoma tissue microarray.
abstract: BACKGROUND
  Aberrant activation of the beta-catenin signaling pathway has been implicated in several malignancies, including breast carcinoma. Recently, it was shown that p53 down-regulated beta-catenin in a complex fashion. The authors examined the expression of beta-catenin, key members of its signaling pathway, and p53 in a large cohort of breast tumors.
  
  
  METHODS
  The authors conducted an immunohistochemical analysis of the expression of beta-catenin, upstream modulators (HER-2/neu, Met, and epidermal growth factor receptor [EGFR]), downstream target genes (cyclin D1 and matrix metalloproteinase-7 [MMP7]), and p53 on a tissue microarray of 346 lymph node-negative breast carcinomas. The results were correlated with one another and with standard clinicopathologic parameters.
  
  
  RESULTS
  beta-Catenin expression was observed in the membrane and/or cytoplasm without any significant nuclear expression. HER-2/neu and EGFR were observed on the membrane in 21% and 6% of tumors, respectively, and Met stained in a membrane/cytoplasm distribution in 28% of cases. Cyclin D1 was expressed in the nucleus and MMP7 was expressed in the cytoplasm in 26% and 75% of tumors, respectively. Nuclear expression of p53 was noted in 31% of tumors. When each marker was analyzed separately, only p53 and Met demonstrated a significant correlation with survival. However, patients who had tumors that coexpressed high levels of beta-catenin and p53 had markedly worse overall survival (P = 0.0026). In multivariate analysis, only tumor size, Met, and the coexpression of beta-catenin and p53 retained statistical significance.
  
  
  CONCLUSIONS
  The current findings support a potential synergistic effect of abnormal beta-catenin regulation and p53 status in the pathogenesis and natural history of lymph node-negative breast carcinoma. Furthermore, the results show that a combined analysis of multiple markers, notably beta-catenin and p53, may enhance the prognostic capabilities compared with individual markers.
authors.affiliation: Section of Medical Oncology, Yale Cancer Center, New Haven, Connecticut 06520, USA. gina.chung@yale.edu
authors.forename: Gina G
authors.initials: GG
authors.lastname: Chung
authors.forename: Maciej P
authors.initials: MP
authors.lastname: Zerkowski
authors.forename: Idris Tolgay
authors.initials: IT
authors.lastname: Ocal
authors.forename: Marisa
authors.initials: M
authors.lastname: Dolled-Filhart
authors.forename: Jung Y
authors.initials: JY
authors.lastname: Kang
authors.forename: Amanda
authors.initials: A
authors.lastname: Psyrri
authors.forename: Robert L
authors.initials: RL
authors.lastname: Camp
authors.forename: David L
authors.initials: DL
authors.lastname: Rimm
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D019938:Cyclin D1 / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D015996:Survival Rate; D015534:Trans-Activators / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D051176:beta Catenin
chemical_list: D014408:Biomarkers, Tumor; D019938:Cyclin D1; D003598:Cytoskeletal Proteins; D066246:ErbB Receptors; D020783:Matrix Metalloproteinase 7; D019859:Proto-Oncogene Proteins c-met; D018719:Erb-b2 Receptor Tyrosine Kinases; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; C495270:CTNNB1 protein, human