ANTERIOR GRADIENT PROTEIN 3 (AGR3) IS ASSOCIATED WITH LESS AGGRESSIVE TUMOURS AND BETTER OUTCOME OF BREAST CANCER PATIENTS

Background:

 Breast cancer is the most common female malignancy and a leading cause of deaths among women worldwide thus understanding molecular mechanisms aff ecting breast cancer patients’ outcome remains of great importance. Anterior gradient protein 3 (AGR3) is a highly related homologue of pro-oncogenic AGR2 and was firstly characterized in breast cancer cell membranes. Its strong expression was shown in various cancers including that of breast, liver, ovary and prostate. However, there is a limiting amount of data depicting AGR3 prognostic relevance in these malignancies.

Material and Methods:

A retrospective cohort of 129 patients with primary breast cancers was selected for the study. Patient age at the time of diagnosis ranged from 29 to 84 years (median 57 years). Immunohistochemical analysis was used to assess the clinical and prognostic significance of AGR3 expression. The immunostaining was evaluated according to the number of positive cells.

 Results:

AGR3 staining was detected in 80% of analyzed specimens. The percentage of AGR3 positive cells statistically significantly correlated with oestrogen receptor (ER), progesterone receptor (PR), as well as low histological grade and inversely correlated with the level of Ki-67 expression. In the whole cohort, AGR3 expression was associated with longer progression free survival (PFS). When pair- -wised with other variables, AGR3-positive subgroup of low histological grade tumours showed significantly longer PFS and overall survival.

Conclusion:

Here, we demonstrate that AGR3 correlates with ER and PR status, slowly proliferating and well-differentiated tumours. AGR3 positivity significantly aff ected longer progression free survival. Our results suggest that AGR3 expression is associated with less aggressive tumours that are more prone to effective treatment and therefore favourable outcome.

The work was supported by MH CZ – DRO (MMCI, 00209805), European Regional Development Fund, the state budget of the Czech Republic for Regional Centre for Applied Molecular Oncology – RECAMO (CZ.1.05/ 2.1.00/ 03.0101), GACR 13-00956S, IGA NT/ 13794-4/ 2012 and the state budget of the Czech Republic (LO1413).