beta-Catenin and p53 analyses of a breast carcinoma tissue microarray

Cancer. 2004 May 15;100(10):2084-92. doi: 10.1002/cncr.20232.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cyclin D1 / metabolism
  • Cytoskeletal Proteins / metabolism*
  • ErbB Receptors / metabolism
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Matrix Metalloproteinase 7 / metabolism
  • Proto-Oncogene Proteins c-met / metabolism
  • Receptor, ErbB-2 / metabolism
  • Survival Rate
  • Trans-Activators / metabolism*
  • Tumor Suppressor Protein p53 / metabolism*
  • beta Catenin


  • Biomarkers, Tumor
  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • Trans-Activators
  • Tumor Suppressor Protein p53
  • beta Catenin
  • Cyclin D1
  • ErbB Receptors
  • Proto-Oncogene Proteins c-met
  • Receptor, ErbB-2
  • Matrix Metalloproteinase 7