Sex-specific differences in the expression levels of estrogen receptor subtypes in colorectal cancer

Background: Altered expression of estrogen receptors alpha and beta (ER alpha and FIR beta) has been hypothesized to play a role in carcinogenesis. However, little is known about the sex-specific differences of ER expression in colorectal cancer (CRC). Objective: This study examined ER alpha and ER beta protein levels in male and female patients with CRC. Methods: Using Western blot analysis, the intensity of ER alpha and FR beta protein levels was determined ill tumor tissue and in corresponding normal colon mucosa from patients with CRC. Results: All 64 white patients (33 men, mean [SEM] age 64.1 [13.1] years, age range 26-90 years; 31 women, mean age 68.5 [14.5] years, age range 39-91. years [4 were premenopausal at time of surgery]) expressed ER alpha and ER beta protein in normal colon mucosa, and there were no significant differences between men and women. In tumor tissue, a significantly increased ER alpha protein level was observed ill men (P = 0.02 vs normal tissue), whereas in women, the ER alpha level did not differ significantly between tumor and normal tissue. The level of ER beta protein in CRC was significantly reduced in both men and women, but more so in men (P = 0.04 vs women). Furthermore, in men, the ER beta level was significantly lower in poorly differentiated tumors than in moderately differentiated tumors (P < 0.03), whereas in women, poor differentiation of the tumor was not associated with a significant decrease of FR beta level. Conclusions: Altered levels of ER subtypes resulting in an increased ER alpha:ER beta ratio were found in patients with CRC. The observation of significantly greater alterations in men than in women Supports the hypothesis of sex-specific differences in the pathogenesis of CRC.