1945

The E-cadherin/catenin system acts as an invasion suppressor of epithelial malignancies. Few studies in the literature have examined the expression of E-cadherin and catenins simultaneously. In this study we measured the expression of E-cadherin, catenins(α-, β-, γ-catenin) and the transcription factors Snail, Slug and Twist in human breast carcinomas using Q-PCR and investigated whether the expression levels were associated with known tumor variables or patient survival(median follow-up 120 months). RNA from frozen sections of breast tissue(tumor n=120, background normal tissue n=33) was reverse transcribed, quantified and analysed by Q-PCR with results expressed as copy number of transcript/50ng RNA(standardized against β-actin). E-cadherin expression was reduced, while α- and β-catenin expression was increased in breast tumors(p=0.064, p=0.079, p=0.140 respectively). E-cadherin expression was reduced in tumors with a moderate or poor prognosis compared to good prognosis tumors(Nottingham Prognostic Index) (good prognosis vs. moderate prognosis p=0.023, good prognosis vs. poor prognosis p=0.15). In contrast, β-catenin expression was increased in tumors with poor prognosis (good prognosis vs. poor prognosis p=0.089, moderate prognosis vs. poor prognosis p=0.036). TNM stage 3 tumors had a significantly reduced E-cadherin expression(Stage 1 vs. 3 p=0.0001, Stage 2 vs. 3 p=0.001). E-cadherin expression in tumors of patients who were disease free was significantly more compared to those with metastatic disease, local recurrence or dying from breast cancer(Disease free vs. poor outcome (metastatic disease and/or local recurrence and/or death from breast cancer) p=0.012). β-catenin expression was increased in patients dying from breast cancer compared to disease free patients and the difference approached statistical significance(p=0.052). Using the same dataset we reported previously that increased expression of Slug and Twist, while reduced expression of Snail may be associated with poor patient prognosis and survival. There was a significant positive correlation between the expression of Twist and α-catenin(p<0.001). Similarly, the expression of Slug and β-catenin was strongly correlated(p<0.001). In conclusion we have shown that quantitative measurement of expression of E-cadherin and β-catenin in human breast cancer was of significant prognostic value in predicting long term outcome of women with breast cancer in this series. The association between β-catenin and Slug, α-catenin and Twist, may represent a novel molecular link connecting cell adhesion and motility. Shutting down the signals mediating this association may be worth considering as a therapeutic approach to cancer invasion and metastasis.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]