title: Evaluation of three commercial progesterone receptor assays in a single tamoxifen-treated breast cancer cohort.
abstract: Estrogen receptor and progesterone receptor status are routinely assessed using immunohistochemistry assays to assist in patient prognosis and clinical management. Three commonly utilized autostainer vendors-Dako, Leica and Ventana-provide ready-to-use progesterone receptor assays; however, they have never been directly compared in a single breast cancer cohort. We looked at three immunohistochemical progesterone receptor assays, in addition to original ligand-binding assay results, in a single retrospective, tamoxifen-treated breast cancer cohort to investigate inter- and intra-observer agreement, concordance, prognostic ability and measures of test performance. All immunohistochemical assays utilized the manufacturer's specified protocols. Five-year disease-free survival was the endpoint of interest, and multivariate models were adjusted for lymph node status, tumor grade, tumor size and human epidermal growth factor 2 status. All assays showed substantial to almost perfect agreement between the three observers (Dako κ=0.69-0.90; Leica κ=0.70-0.89; and Ventana κ=0.78-0.94) and concordance (Dako/Leica κ=0.81; Dako/Ventana κ=0.78; and Leica/Ventana κ=0.82). Univariate survival analyses showed that only the ligand-binding assay, Dako and Ventana assays achieved statistical significance. No statistically significant results were seen in multivariate models, although a strong trend was seen with the Ventana progesterone receptor assay. All assays performed similarly with regards to measures of test performance with ligand-binding assay set as the reference, and all immunohistochemical assays outperformed the ligand-binding assay in regards to 5-year disease-free survival. Despite similar agreement and concordance with the progesterone receptor assays, clear differences were noted with regards to 5-year disease-free survival. Additional survival analyses suggest that clinical utility of estrogen receptor assays vary when investigated in combination with progesterone receptor.
authors: Translational Laboratories, Tom Baker Cancer Centre, Alberta Health Services, Calgary, Alberta, Canada.
authors: Elizabeth N
authors: EN
authors: Kornaga
authors: Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT, USA.
authors: Alexander C
authors: AC
authors: Klimowicz
authors: Translational Laboratories, Tom Baker Cancer Centre, Alberta Health Services, Calgary, Alberta, Canada.
authors: Natalia
authors: N
authors: Guggisberg
authors: Department of Pathology, Calgary Laboratory Services, Calgary, Alberta, Canada.
authors: Travis
authors: T
authors: Ogilvie
authors: Translational Laboratories, Tom Baker Cancer Centre, Alberta Health Services, Calgary, Alberta, Canada.|Department of Oncology, Tom Baker Cancer Centre and University of Calgary, Calgary, Alberta, Canada.
authors: Don G
authors: DG
authors: Morris
authors: Department of Oncology, Tom Baker Cancer Centre and University of Calgary, Calgary, Alberta, Canada.
authors: Marc
authors: M
authors: Webster
authors: Department of Anatomic Pathology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors: Anthony M
authors: AM
authors: Magliocco
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D053208:Kaplan-Meier Estimate; D015588:Observer Variation; D016016:Proportional Hazards Models; D011933:Reagent Kits, Diagnostic; D011980:Receptors, Progesterone / Q000032:analysis*; D012189:Retrospective Studies; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use; D013629:Tamoxifen / Q000627:therapeutic use
chemical_list: D014408:Biomarkers, Tumor; D011933:Reagent Kits, Diagnostic; D011980:Receptors, Progesterone; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen