Beta-catenin has a crucial role in cell-cell adhesion as well as a signaling role as a member of the Wnt pathway. The aim of this study was to examine the clinicopathological and prognostic value of phosphorylated
beta-catenin, as well as its relation to the
tumors' phenotype, in
breast cancer. Immunohistochemistry was applied on 141
paraffin-embedded breast tissue specimens for the detection of phospho-
beta-catenin, ER, PR, c-erbB-2, p53, Ki-67, bcl-2, uPAR and
TIMP-1. For each case, a phospho-
beta-catenin index was determined by image analysis. Phospho-
beta-catenin staining was detected in the cytoplasm and the nucleus of the malignant cells. Cytoplasmic phospho-
beta-catenin was statistically higher in
carcinomas of smaller
tumor size (P = 0.030), lower stage (P = 0.026), decreased Ki-67 and high c-erbB-2 immunoreactivity (P = 0.052 and P = 0.037, respectively). Nuclear phospho-
beta-catenin showed a parallel correlation with ER and
ERbeta (P = 0.022 and P = 0.043, respectively), bcl-2 (P = 0.042), uPAR in
cancer cells (P = 0.041) and
TIMP-1, although the correlation was borderline (P = 0.066). Cytoplasmic phospho-
beta-catenin was found to be independently correlated with prolonged disease-free and overall survival (P = 0.046 and P = 0.002, respectively), whereas nuclear localization was correlated with a shortened overall survival (P = 0.046). In conclusion, phospho-
beta-catenin may have a different involvement in invasive
breast carcinomas, according to its subcellular distribution. Nuclear localization seems to be related to an aggressive
tumor phenotype, negatively affecting patients' overall survival, whereas cytoplasmic localization is associated with a favorable
tumor phenotype and a longer disease-free and overall survival.