We have recently shown that breast cancer tissue cultures with higher levels of progesterone receptor isoform A (PRA) than isoform B (PRB) were inhibited by antiprogestins. This highlights the relevance of determining the PRA/PRB ratio to identify patients that may benefit from this therapy. The aim of this study was to evaluate the concordance between the PR isoform ratio determined by western blots (WB) in core biopsies and in surgical samples from the same breast cancer patients (n=48) from the Hospital “Magdalena V Martínez” from General Pacheco, Buenos Aires. The protocol has been approved by Institutional Review Boards.
We determined the PRA/PRB ratio by WB using nuclear extracts from frozen tissues (biopsy and surgery) and the percentage of cells expressing PR measured by immunohistochemistry (IHC) was obtained from the clinical records (surgical samples). The analysis of the concordance between the core biopsy and surgical categorization was performed using the Cohen's Kappa coefficient. To categorize samples according to the PRA/PRB ratio, we considered samples enriched in PRA (PRA-H) those with PRA/PRB ≥ 1.2, those enriched in PRB, (PRB-H) with PRA/PRB ≤ 0.83, and equimolar (EQUI) samples, those with ratios in between 1.2 and 0.83.
A 93% of coincidence was observed between WB and IHC data. The discordant samples had low PR levels determined by IHC (<20%) and proved negative in WB. When these 3 groups of PR+ samples, together with PR negative samples, were analyzed comparing the core biopsy and the surgical categorization, a 77% of concordance and a Kappa coefficient of 0.637 (N=48, p< 0.01) was obtained. However, when PR+ cases in which an agreement with the IHC and the WB data was observed, this value rose to 0.724 (N=18, p<0.01).
This study indicates that the PR isoform categorization from core biopsy specimens reflects the PRA/PRB ratio in the tumor in cases in which PR status observed by IHC and WB from biopsy cores are coincident suggesting the possible use of this tool to potentially predict antiprogestin response in case of neoadjuvant treatment.