Analysis of the potential contribution of estrogen receptor (ER) β in ER cytosolic assay of breast cancer

✍ Scribed by J.P. Brouillet; M.A. Dujardin; D. Chalbos; J.M. Rey; J. Grenier; P.J. Lamy; T. Maudelonde; P. Pujol

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: French
• Weight: 84 KB
• Volume: 95
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/1097-0215(20010720)95:4<205::aid-ijc1035>3.0.co;2-y

✦ Synopsis

Estrogen receptor (ER) content is the most useful parameter for predicting hormone response therapy in breast cancer. Assays available for detecting ER in breast tumor cytosol are ligand-binding assay (LBA), which detects both ER␣ and ER␤, and the enzymatic immunoassay (EIA), in which monoclonal antibodies are directed against ER␣. As shown in several studies, the 2 assays correlate and both are used routinely. However, some discrepancies between the 2 assays were found and explanations remain controversial. We evaluated ER␣ and ER␤ mRNA coexpression in breast tumors in order to study whether the presence of ER␤ could account for differences between LBA and EIA in the determination of ER protein level. Using HeLa cell lines transfected with either ER␣ or ER␤, we confirmed that EIA, using H222 and D547 monoclonal antibodies, recognizes only ER␣ expression, whereas LBA detects both isoforms. In 119 breast tumor cytosols, the correlation between ER-EIA and ER-LBA was high (r ‫؍‬ 0.72), although some discrepancies were found. When analyzing ER mRNA expression of samples with higher LBA values, no overexpression of ER␤ mRNA relatively to ER␣ mRNA were observed. There was a difference in ER␤/ ER␣ ratio between ER-negative and ER-positive samples, with a 10-fold increased median ratio in ER-negative samples (p ‫؍‬ 0.01). We thus confirmed that the major form of ER in breast cancer is the ER␣ at both the protein and mRNA levels. Moreover, our data do not support the hypothesis that ER␤ expression could explain differences between LBA and EIA in the determination of ER protein level.