Estrogen Receptor β Isoforms 1, 2 and 5 and Oncotype Recurrence Score
A Fung, A Adams, A Page, D Williams, C Cohen. Emory University Hospital, Atlanta, GA
Background: The use of selective estrogen receptor modulators (SERMs) is a mainstay of breast carcinoma treatment. The ER receptor is a member of the steroid/thyroid nuclear receptor superfamily and is composed of an α and β subtype. The β subtype is further subdivided into five isoforms, ERβ1 through ERβ5. Isoforms ERβ1, ERβ2, ERβ4 and ERβ5 are breast specific while ERβ3 is testes specific. When evaluated in breast carcinoma, ERβ1 showed no association with disease outcome, while ERβ2 and ERβ5 correlated with improved relapse-free survival. ERβ2 is felt to be a prognostic indicator in breast carcinoma and is postulated to play a role in carcinogenesis. Oncotype DX is a reverse transcriptase polymerase chain reaction (RT-PCR) assay that predicts ten year risk of recurrence in lymph node negative ER-positive breast carcinomas. It utilizes the expression of twenty-one genes to give a Recurrence Score from 0-100. Patients are stratified into three risk categories; low (0-17), intermediate (18-30) and high risk (31+) of recurrence based on the Recurrence Score.
Design: One hundred thirty patients with known positivity for estrogen receptor alpha (ERα) and Recurrence Score available, were selected. Immunohistochemistry for ERβ1, ERβ2 and ERβ5 were each performed on three tissue microarrays with two 1mm cores of each tumor. Less than ten percent expression was used as the negative cutoff for each value. Results were compared to Recurrence Scores.
Results: Three percent of the carcinomas were ERβ1 positive, forty-eight percent were ERβ2 positive and sixty-six percent were ERβ5 positive.
|Oncotype Low||Oncotype Intermediate||Oncotype High||p-value|
|ER β 1||2/130 = 1.5%||2/130 = 1.5%||0/130 = 0%||0.1667|
|ER β 2||39/130 = 30%||21/130 = 16%||3/130 = 2.3%||0.0000|
|ER β 5||46/130 = 35.4%||33/130 = 25.4%||7/130 = 5.4%||0.0000|