G-protein-coupled receptor GPR30 expression as a prognostic factor in breast cancer patients

Purpose: GPR30 is a member of the superfamily of G-protein-coupled receptors and mediates rapid „non-classic” estrogen actions. This study was performed to examine GPR30 protein expression in breast cancer specimens and normal breast tissue. Furthermore, we investigated the prognostic value of GPR30 in breast cancer patients. Methods: GPR30 protein expression was examined immunohistochemically in 164 primary breast cancer specimens and their matched normal breast epithelium and this relationship was correlated to different clinicopathological characteristics. Additionally, GPR30 expression was examined in 38 ductal carcinoma in situ and 31 synchronous breast cancer metastases. Results: The mean level of GPR30 expression and its variation during breast cancer progression remained relatively constant. However, a decrease of GPR30 expression in breast cancer tissue, compared to normal tissue, was associated with poor overall survival (p = 0.043) and disease-free survival (p = 0.037). The 5-year overall survival was 83.1% for patients with decreased GPR30 expression vs. 91.9% for patients with increased or unchanged GPR30- protein expression. GPR30 down-regulation correlated significantly with increased histological grading (p = 0.015), lymph node metastases (p = 0.032) and negative estrogen receptor status (p = 0.018). The down-regulation of GPR30 expression remains a significant prognostic factor in multivariate analysis for DFS (HR = 1.569; 95% CI, 1.024 – 2.797; p= 0.041) and OS (HR = 2.082; 95% CI, 1.248 – 4.773; p = 0.039). These results were confirmed in a second independent group of 95 triple-negative breast cancer patients.

Conclusions: Aberrant GPR30 expression seems to be an important prognostic factor in breast cancer patients. Its role as a target for treatment has to be investigated.