1. ¹Department of Pathology, Attikon Hospital, Athens, Greece
2. ²Department of Pathology, School of Medicine, National and Kapodistrian University of Athens, Goudi, Athens, Greece
3. ³Department of Pathology, Alexandra Hospital, Athens, Greece

Correspondence: Dr L Nakopoulou, MD, PhD, Department of Pathology, School of Medicine, National and Kapodistrian University of Athens, 75 Mikras Asias Street, Goudi, GR-11527 Athens, Greece. E-mail: lnakopou@cc.uoa.gr

Received 27 September 2005; Revised 5 January 2006; Accepted 5 January 2006; Published online 10 February 2006.

Abstract

-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 -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--catenin, ER, PR, c-erbB-2, p53, Ki-67, bcl-2, uPAR and TIMP-1. For each case, a phospho--catenin index was determined by image analysis. Phospho--catenin staining was detected in the cytoplasm and the nucleus of the malignant cells. Cytoplasmic phospho--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--catenin showed a parallel correlation with ER and ER (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--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--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.