PT  - JOURNAL ARTICLE
AU  - López-Knowles, Elena
AU  - Zardawi, Sarah J.
AU  - McNeil, Catriona M.
AU  - Millar, Ewan K.A.
AU  - Crea, Paul
AU  - Musgrove, Elizabeth A.
AU  - Sutherland, Robert L.
AU  - O'Toole, Sandra A.
TI  - Cytoplasmic Localization of β-Catenin is a Marker of Poor Outcome in Breast Cancer Patients
AID  - 10.1158/1055-9965.EPI-09-0741
DP  - 2010 Jan 01
TA  - Cancer Epidemiology Biomarkers & Prevention
PG  - 301--309
VI  - 19
IP  - 1
4099  - http://cebp.aacrjournals.org/content/19/1/301.short
4100  - http://cebp.aacrjournals.org/content/19/1/301.full
SO  - Cancer Epidemiol Biomarkers Prev2010 Jan 01; 19
AB  - β-catenin is involved in cell adhesion through catenin-cadherin complexes and as a transcriptional regulator in the Wnt signaling pathway. Its deregulation is important in the genesis of a number of human malignancies, particularly colorectal cancer. A range of studies has been undertaken in breast cancer, with contradictory associations reported among β-catenin expression, clinicopathologic variables, and disease outcome. We undertook an immunohistochemical study measuring the levels and subcellular localization of β-catenin in 292 invasive ductal breast cancers with known treatment and outcome. No association with breast cancer–specific death was observed for cytoplasmic or membrane expression alone; however, a continuous score representing both locations (membrane minus cytoplasmic expression: MTC score) was associated with a worse outcome in univariate analysis (P = 0.004), and approached significance in a multivariate analysis model that included lymph node, progesterone receptor (PR), and HER2 status (P = 0.054). Therefore, the MTC score was used for further statistical analyses due to the importance of both the subcellular location and the levels of expression of β-catenin. An association was identified between high cytoplasmic expression (low MTC score), and high tumor grade (P = 0.004), positive Ki67 (P = 0.005), negative estrogen receptor (ER) (P = 0.005), positive HER2 (P = 0.04) status, and an active phosphoinositide 3-kinase pathway (P = 0.005), measured as PIK3CA mutations (P = 0.05) or PTEN loss (P = 0.05). Low cytoplasmic expression (high MTC score) was associated with the luminal A subtype (P = 0.004). In conclusion, a low β-catenin MTC score is associated with an adverse outcome in breast cancer, which may be of mechanistic significance in the disease process. Cancer Epidemiol Biomakers Prev; 19(1); 301–9