Interaction between estrogens and androgen receptor genes microsatellites, prostate-specific antigen and androgen...

The role of estrogen and androgen receptors signaling in breast cancer is widely accepted, but the interrelations between them are not well understood. It was suggested that PSA could be a marker of endogenous balance between androgens and estrogens. In this context, we intended to investigate the potential of relationship between polymorphic tandem repeats (CAG, TA and CA) in AR (androgen receptor), ERalpha (estrogen receptor alpha) and ERbeta (estrogen receptor beta) genes and the immunoexpression of PSA and AR proteins. We assessed also the possible influences of CAG, TA, and CA variables and other available prognostic factors (ER, PR, AR, HER2/neu, PSA expression, and nodal status) on disease-free survival. We assessed the polymorphic tandem repeats lengths by genotyping, followed by high-resolution denaturing polyacrylamide gel electrophoresis in 163 breast cancers. Immunohistochemistry was performed to assess the expressions of AR, PSA, ER, PR and HER2/neu proteins. Our results showed that PSA was correlated with the length of CA repeats in the 3'-untranslated region of ERbeta, shorter CA repeats being correlated with PSA expression (p=0.03). AR immunoexpression was correlated with CAG repeats on AR gene, higher number of repeats being linked to a higher AR immunoexpression (p=0.04). Performing logistic regression to investigate relationships with prognosis, we observed that PSA immunoexpression (p=0.004), the nodal status (p-<0.001) and marginally, longer TA repeats (p=0.05) were correlated with increased disease-free survival. AR expression presented a low statistical value (p=0.054) in predicting evolution and was not entered into the multivariate regression analysis. Altogether, our findings supports the hypothesis that estrogens, through both alpha and beta-receptors variants are mediating the AR signaling pathway.