title: 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.
authors.affiliation: a Department of Biosciences and Nutrition , Karolinska Institutet , Huddinge , Sweden.
authors.forename: Muhammad Sharif
authors.initials: MS
authors.lastname: Hasni
authors.affiliation: a Department of Biosciences and Nutrition , Karolinska Institutet , Huddinge , Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Berglund
authors.affiliation: a Department of Biosciences and Nutrition , Karolinska Institutet , Huddinge , Sweden.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Yakimchuk
authors.affiliation: a Department of Biosciences and Nutrition , Karolinska Institutet , Huddinge , Sweden.
authors.forename: Jiyu
authors.initials: J
authors.lastname: Guan
authors.affiliation: b Department of Clinical Sciences, Division of Oncology and Pathology , Lund University, Skåne University Hospital , Lund , Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Linderoth
authors.affiliation: c Division of Clinical and Experimental Pathology, Department of Immunology, Genetics and Pathology , Rudbecklaboratoriet, Uppsala University , Uppsala , Sweden.
authors.forename: Rose Marie
authors.initials: RM
authors.lastname: Amini
authors.affiliation: d Division of Experimental and Clinical Oncology, Department of Immunology, Genetics and Pathology , Rudbecklaboratoriet, Uppsala University , Uppsala , Sweden.
authors.forename: Gunilla
authors.initials: G
authors.lastname: Enblad
authors.affiliation: a Department of Biosciences and Nutrition , Karolinska Institutet , Huddinge , Sweden.
authors.forename: Sam
authors.initials: S
authors.lastname: Okret
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D004195:Disease Models, Animal; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012737:Sex Factors; D016019:Survival Analysis; D016896:Treatment Outcome; D047368:Tumor Burden / Q000235:genetics; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D047629:Estrogen Receptor beta
keywords: Estrogen; gender difference; immunohistochemistry; lymphoma growth; receptor expression