1013 Background: Recently, we have confirmed that HAGE is involved in promoting proliferation as assessed by increased thymidine incorporation and our preliminary results using shRNA to permanently knockdown HAGE expression also suggests the involvement of HAGE in tumor motility and metastasis. In this study we aimed to analyze the expression of HAGE in large well-characterized BC cohorts to determine its relationship with other clinico-pathological parameters and to investigate its prognostic value. Methods: HAGE protein expression was assessed in: a) 40 normal breast tissue (NBT), b) 60 invasive BCs and their matching NBT, c) BC cell lines, d) A series of 1650 consecutive cases of primary BC who treated with adjuvant CMF and/or endocrine therapies. Further validation was performed in 2 independent series of high risk ER- BC: a) 300 ER –BC who did not received any CT and b) 396 ER- BC treated with adjuvant anthracycline (ATC) based CT. Results: The NBT showed negative HAGE expression (HAGE-) throughout. HAGE overexpression (HAGE+) was observed in 10% of BC and was significantly associated with aggressive clinico-pathological features including: ER-, high grade and triple negative phenotypes. Moreover, HAGE+ expression showed an adverse outcome with a 2-4 fold increase in the risk of death, recurrence and metastases (ps<0.00001) compared to HAGE-; ps<0.0001. Using a multivariate Cox regression model including ER status, grade, size and tumour stage, HAGE expression was confirmed as a powerful independent prognostic factor (p<0.0001). The poor clinical outcome of HAGE+ was further confirmed in high risk (NPI>3.4) ER- patients who did not received any CT (p<0.0001). While, adjuvant CT either CMF or ATC had a positive impact on HAGE+/high risk ER- BC as HAGE+ had a similar risk of death, recurrence and distant metastases to HAGE- expression. Conclusions: This is the first report which shows HAGE to be a potential predictor for poor prognosis in BC patients, and may be an attractive novel target for molecular and vaccine therapy for those patients. A prospective trial of adjuvant chemotherapy/vaccine to confirm this finding is warranted.
c-Flip protein expression in Burkitt's lymphomas is associated with a poor clinical outcome
