Combined Estrogen Alpha and Beta Receptor Expression Has a Prognostic Significance for Colorectal Cancer Patients

We reported that high estrogen receptor beta (ER beta) expression is independently associated with better prognosis in female colorectal cancer (CRC) patients. However, estrogen receptor alpha (ER alpha) is expressed at very low levels in normal colon mucosa, and its prognostic role in CRC has not been explored. Herein, we investigated the combined role of ER alpha and ER beta expression in the prognosis of female patients with CRC, which, to the best of our knowledge, is the first study to investigate this topic. A total number of 306 primary CRCs were immunostained for ER alpha and ER beta expression. A Cox regression model was used to evaluate overall survival (OS) and disease-free survival (DFS). The combined expression of high ER beta + negative ER alpha correlates with longer OS (HR = 0.23; 95% CI: 0.11-0.45, P <0.0001) and DFS (HR = 0.10; 95% CI: 0.03-0.26, P < 0.0001) and a more favorable tumor outcome, as well as significantly higher expression of antitumorigenic proteins than combined expression of low ER beta + positive ER alpha. Importantly, we found that low ER beta expression was associated with local recurrence of CRC, whereas ER alpha expression was correlated with liver metastasis. Overall, our results show that the combined high ER beta + negative ER alpha expression correlated with a better prognosis for CRC patients. Our results suggest that the combined expression of ER alpha and ER beta could be used as a predictive combination marker for CRC patients, especially for predicting DFS.