Independent characterization by duel staining of progesterone receptor (PR) and estrogen receptor (ER) in breast cancer (BC).

Abstract

596 Background: The oncology literature indicates that ER and PR are linked and in BC the presence of PR usually indicates functional ER. BCs express both ER and PR to varying degree, but little has been published on expression of ER + PR in individual cancer cells. The goal of this study is to 1. Determine the expression ER and PR at the cellular level, 2. Determine if ER and PR are expressed in the same BC cells. If ER and PR are separate, this may indicate that antiestrogens and antiprogestins may target different cells. Methods: Archived 1° BC specimens were processed using standard IHC techniques for ER/PR testing. The procedure consisted of sequential double staining on the same microtone section, where the PR was visualized through brown staining using HRP/DAB, and the ER was visualized through red staining using AP/Permanent Red. The initial testing on 13 tumor samples utilized a duel anti-PR-A/B antibody (Ab) and an ER Ab. The next 63 tumor samples utilized; 1. anti-ER and anti-PR-A Abs, 2. anti-ER and anti-PR-B Abs. A pathologist experienced with IHC, interpreted and enumerated the cells staining positive for ER only, for PR only and cells staining positive for both ER & PR. The number of cells expected to be stained for both ER & PR by chance can be calculated as the rate of total ER by the rate of total PR and compared with the observed rate (paired rank test). ER/PR positivity is defined as ≥ 5% cells positive. Results: In the first series, 11/13 tumors were ERpos, 13/13 were PRpos, 7/13 tumors had both ER & PR expressed in 5-20% (median 5%) of the same tumor cells. In the 2nd series of 63 tumors; 1. 50/53 were ERpos, 52/53 were PRApos and 44/53 had both ER & PRA expressed in <5-20% (median 5%) of the same tumor cells, 2. 44/52 were ERpos, 52/52 were PRBpos and 42/52 tumors had both ER & PRB expressed in <5-20% (median 10%) of the same tumor cells. Areas of ER or PR only predominance were frequent. A paired rank test indicates that the observed rate (median 9%) of ER/PR duel staining is less than predicted (median 18%, p <0.000). Conclusions: ER & PR were expressed in the majority of tumors examined with a minority the tumor cells expressing both ER & PR. These data support evaluating antiprogestins as a different therapeutic target from ER.