Progesterone receptor is a
surrogate marker of
estrogen receptor activity in
breast cancer and its utility in helping predict clinical outcome has been established using biochemical assays. However, most laboratories worldwide have switched to immunohistochemistry to assess
progesterone receptor, but unfortunately no validated immunohistochemical assay exists for
progesterone receptor. The purpose of this study was to develop and validate an immunohistochemical assay for
progesterone receptor in
breast cancer. The assay was based on
monoclonal antibody 1294 (DakoCytomation) and slides were scored microscopically using the 'Allred score' on a scale of 0-8. The assay was compared to
ligand-binding assay in 1235 breast
cancers, and a subset (n=362) that received only hormonal
therapy was used to define a cutoff for
progesterone receptor-positive. Clinical utility was validated in an independent set of samples (n=423) from a clinical trial randomizing premenopausal
breast cancer patients to tamoxifen+oophorectomy vs observation following surgery. A cutoff of >2 (corresponding to >1% positive cells) dichotomized patients with significantly better or worse clinical outcome (P=0.0014).
Progesterone receptor by immunohistochemistry provided significantly better results than
progesterone receptor by
ligand-binding assay in predicting clinical outcome. In the clinical trial, a positive result in univariate analyses was associated with significantly improved disease-free and overall survival both in untreated (hazard ratios/P=0.656/0.060 and 0.479/0.005, respectively) and hormonally treated patients (hazard ratios/P=0.529/0.017 and 0.451/0.007, respectively). Positive
progesterone receptor remained significant for improved disease-free and overall survival (hazard ratios/P=0.666/0.038 and 0.549/0.007, respectively) in multivariate analyses including the standard variables of
tumor size, nodal status, treatment, histological grade, and HER-2/neu status.
Estrogen and
progesterone receptors are codependent variables and
progesterone receptor was a weaker predictor of response to endocrine
therapy than
estrogen receptor when both were included in multivariate analysis. This is the first comprehensive study assessing the clinical usefulness of
progesterone receptor by immunohistochemistry in archival tissue in
breast cancer.
Progesterone receptor assessed by immunohistochemistry provides useful information about clinical outcome and it is better than
progesterone receptor measured by
ligand-binding assay.