Abstract P5-02-13: Triple negative breast cancer, the impact of isotype-specific progesterone receptor antibodies on the diagnosis results
Authors: Bonneterre Jacques , Bosq Jacques , Alleaume Charline , Gilles Erard , Jamme Philippe , Zukiwski Alexander 
Published: May 2015

Abstract
Background: Given the poor therapeutic outcomes for triple negative breast cancer (TNBC), diagnostic accuracy is vital. In routine IHC testing, the progesterone receptor (PR) is determined using bispecific antibodies (Ab) that recognize epitopes common to PRA and PRB. PRA and PRB expression can be imbalanced in BC. Relative expression of the PR isotypes appears to be prognostic in BC evaluated with a bispecific Ab (Hopp 2004). Tumors can express PRA or PRB on different cells in the same tumor (Mote 2008), which differs from those expressing ERα (Zukiwski 2013). A true TN phenotype might escape detection with the use of one single Ab to detect both PRA and B epitopes, depending on sensitivity/specificity. This study evaluated the use of two isotype-specific PR Abs to fully characterize the PR status.
Methods: 83 dual ERα and HER2 negative archived BC specimens with clinical data were obtained from the Oscar Lambret Cancer Center, Lille, FR. IHC was performed using anti-PRA, anti-PRB, and the bispecific anti-PR Pg636 antibodies. PR tumor positivity was explored using 2 cut-offs, ≥ 1% or ≥ 5% stained tumor cells. PR positive tumors were defined as either PRA or PRB positive.
Results: For PR positive tumors with ≥ 1% positive cells, average PRA positivity was 41%, PRB was 38% (PRA vs PRB p = NS), and PRAB 3% (PRA vs PRAB = 0.001, PRB vs PR AB p = 0.0001). Using 1% as positivity cut off PRA and PRB were discordant in 14% of the cases, PRA and PR AB in 12%. PR B and PR AB were discordant in 2%. Discordance between PR positivity (either A or B) and PRAB positivity was 7% with no PR negative PRAB positive tumors i.e. no positivity was missed using two PR A and B antibodies while all 7% cases were missed by the PRAB antibody. Using 5% as a cut off, the discordance rate was 8% between PRA and PRB, 25% between PRA and PRAB and no PRA negative and PRAB positive case were found, and 26% between PRB and PRAB with no PRB negative PRAB positive cases either. PR positivity (A or B) was missed in 30% of the cases with a PRAB. Patients with tumors identified as PR positive (≥ 5%) using the isotype specific antibodies and PR negative with the PRAB antibody have a better prognosis (DFS).
Conclusion: In TNBC, there is a different staining pattern when using isotype-specific vs bispecific anti-PR anti-bodies. The average percent of positive tumors cells is substantially reduced when using a bispecific Ab as compared to isotype-specific AB. This translates into potential false negative PRAB testing which varies from 7% to 30% depending of the cut off criteria. TNBC reclassified by the use of isotype-specific anti-PR antibodies may be appropriate for investigation with anti-progestins.
Citation Format: Jacques Bonneterre, Jacques Bosq, Charline Alleaume, Erard Gilles, Philippe Jamme, Alexander Zukiwski. Triple negative breast cancer, the impact of isotype-specific progesterone receptor antibodies on the diagnosis results [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-02-13.