Pogesterone Receptor (PgR) Protein but Not mRNA Is Associated with Better Outcome in Tamoxifen Treated Breast Cancer Patients
Kurt A Schalper, Kevin Li, Elizabeth Zarrella, David L Rimm. Yale University, New Haven, CT
Background: ERα and PgR protein are frequently co-expressed in breast carcinomas and their levels are positively associated with better patient outcome. PgR protein expression has been shown to be independently predictive of response to hormonal therapy, but some studies suggest its specific for ERα. Less is known about mRNA. Data using both RT-PCR (Kim et al, 2011 JCO) and quantitative in situ mRNA hybridization (qISH) (Bordeaux et al., 2012, PLoS One) show that ESR1 mRNA levels may be predictive of response to endocrine therapy in a manner that is different from ERα protein. Here we assess the prognostic and predictive properties of PgR mRNA.
Design: PgR protein and mRNA were measured on formalin fixed paraffin embedded (FFPE) tumor samples on two cohorts represented on tissue microarrays (TMA). Cohort 1 represents a retrospective cohort of 404 breast carcinomas collected from the Yale Pathology archives between 1975 and 2005. Cohort 2 was constructed from 260 breast carcinomas, most of them between 2000 and 2009. PgR protein was measured using the mouse monoclonal clone PGR636 (DAKO). ERα was measured with the rabbit monoclonal clone SP1 (Thermo scientific). The RNAscope paired-primer method was used for PgR mRNA qISH with Ubiquitin C and DapB ISH probes were used as positive and negative controls for each run. PgR protein and mRNA were measured using the AQUA method of quantitative fluorescence.
Results: In both cohorts PgR protein scores showed a positive non-linear association with PgR mRNA levels (Cohort 1 R2=0.12, P<0.001; Cohort 2 R2=0.59, P= P<0.0001). PgR protein and mRNA levels were also concordant to pathologist readings of PgR status. Neither PgR protein or mRNA levels were prognostic in Cohort 1. However, positive PgR protein using a visually defined threshold was associated with better outcome only in Tamoxifen treated patients and this effect was independent from ERα levels (Log Rank p=0.009). PgR mRNA was not predictive for response to Tamoxifen.
Conclusions: Our data show that elevated PgR protein but not in situ PgR mRNA levels may be predictive of favorable response to endocrine therapy in breast carcinomas. Validation in larger independent cohorts is required.
Monday, March 4, 2013 9:00 AM
Proffered Papers: Section B, Monday Morning