ERM/Rho protein expression in ductal breast cancer: a 15 year follow-up

PURPOSE: The aim of this study was to examine the expression of ERM (ezrin, moesin) and Rho (RhoA, RhoB and Cdc42) proteins in breast cancer (BC) patients and to investigate the relationship between the sub-cellular localisation of these proteins and clinicopathological characteristics and patient survival. METHODS: The expression and specific sub-cellular distribution of the ERM/Rho proteins was analysed by immunohistochemistry in a homogeneous group of 85 stage II ductal BC patients with a follow-up of 15 years. RESULTS: Enhanced immunoreactivity of all analysed proteins was found to be associated with the presence of lymph node metastases (ezrin, P = 0.047, moesin, P = 0.038, RhoA, P = 0.024, RhoB, P = 0.004 and Cdc42, P = 0.047). Nuclear localisation of ezrin was found to correlate with the presence of lymph nodes metastases (P = 0.004) and with histological de-differentiation (P = 0.015). In contrast, we found that the nuclear topography of RhoA and Cdc42, and the perinuclear localisation of RhoB, were strongly associated with a lack of nodal metastases (P = 0.008, P = 0.048, P = 0.001, respectively), whereas a decreased reactivity of RhoA in the stromal compartment of BC tumours was associated with the presence of lymph node metastases (P = 0.011). No relationship was observed between ERM/Rho protein expression and oestrogen receptor (ER), progesterone receptor (PgR) or HER-2 reactivity in the BC cells. Also, ERM/Rho protein expression did not predict patient survival, but RhoB over-expression in the stromal compartment of the tumours was found to be associated with a better prognosis (P = 0.0106). CONCLUSIONS: The ERM/Rho immunoprofile and the assessment of its specific sub-cellular localisation may be instrumental for the prediction of lymph node metastases in ductal BC patients.