Significance of the metastasis-inducing protein AGR2 for outcome in hormonally treated breast cancer patients

The anterior gradient protein-2 (AGR2) is inducible by oestrogen and itself can induce metastasis in a rat model for breast cancer. Here, a rabbit antibody to recombinant human AGR2 was used to assess its prognostic significance in a retrospective cohort of 351 breast cancer patients treated by adjuvant hormonal therapy. The antibody stains 66% of breast carcinomas to varying degrees. The percentage of positive carcinoma cells in tumours directly correlates with the level of AGR2 mRNA (Spearman's rank correlation, P=0.0007) and protein (linear regression analysis r(2)=0.95, P=0.0002). There is a significant association of staining of carcinomas for AGR2 with oestrogen receptor α (ERα) staining and with low histological grade (both Fisher's Exact test P<0.0001). In the ERα-positive cases, but not the ERα-negative cases, when subdivided into the separate staining classes for AGR2, there is a significantly progressive decrease in patient survival with increased staining (log rank test, P=0.006). The significant association of staining for AGR2 with patient death over a 10-year period (log rank test P=0.007, hazard ratio=3) only becomes significant at 6 years of follow-up. This may be due to the cessation of adjuvant hormonal therapy at an earlier time, resulting in adverse re-expression of the metastasis-inducing protein AGR2.