Estrogen receptor β1 in diffuse large B-cell lymphoma growth and as a prognostic biomarker

Abstract

Diffuse large B-cell lymphoma (DLBCL) shows a higher incidence in males versus females. Epidemiological studies have shown that female gender is a favorable prognostic factor, which may be explained by estrogens. Here we show that when grafting human DLBCL cells to immunocompromised mice, tumor growth in males is faster. When treating mice grafted with either germinal center or activated B-cell like DLBCL cells with the selective estrogen receptor β (ERβ) agonist diarylpropionitrile, tumor growth was significantly inhibited. Furthermore, nuclear ERβ1 expression analysis in primary DLBCL’s by immunohistochemistry revealed expression in 89% of the cases. Nuclear ERβ1 expression was in a univariate and multivariate analysis, an independent prognostic factor for adverse progression-free survival in Rituximab-chemotherapy treated DLBCL (p = 0.02 and p = 0.04, respectively). These results suggest that estrogen signaling through ERβ1 is an interesting future therapeutic target for treatment of DLBCL, and that ERβ1 expression can be used as a prognostic marker.

Keywords:

• Estrogen
• gender difference
• immunohistochemistry
• lymphoma growth
• receptor expression

Acknowledgements

We thank Dr. Gustaf Hedström for help with statistical analysis. This project has been supported by funds from the Swedish Cancer Society, AFA Insurance, The Swedish Childhood Cancer Foundation, Karo Bio Research Foundation, all to SO, and by Erik, Karin and Gösta Selanders Foundation to GE.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at http://dx.doi.org/10.1080/10428194.2016.1193853.