TAMOXIFEN AZIRIDINE LABELING OF THE ESTROGEN-RECEPTOR - POTENTIAL UTILITY IN DETECTING BIOLOGICALLY AGGRESSIVE BREAST-TUMORS

Expression of estrogen receptor (ER) is a helpful predictor of respons e to endocrine therapy and disease free survival in breast cancer pati ents. The presence of variant estrogen receptors has been demonstrated at the RNA/DNA level and might represent an escape of tumors from hor monal control mechanisms, However, the demonstration that the correspo nding peptides do exist is a real challenge. Denaturing polyacrylamide gel electrophoresis (SDS-PAGE) of covalently bound [H-3]tamoxifen azi ridine ([H-3]TAZ) to ER demonstrates a specific, multiband peptide pat tern recognized by anti-ER monoclonal antibodies (anti-ER Mo Abs). The native 66 kDa ER form identified through its hormone binding domain b y the H-222 Mo Ab was the most prominent one followed by 50, 35, and 2 8 kDa forms on fluorography. Such patterns from early human breast tum ors were compared to the ones of more advanced disease, namely large p rimary breast cancers, metastatic lymph nodes: and soft tissue relapse s: in these cases, molecular forms of 43 and 35 kDa were identified wi th a remarkable consistency. The 43 kDa peptide was more frequently id entified by the H-226 Mo Ab (which maps a region near the DNA binding domain) - albeit with low labeling intensity as compared to H-222 Mo A b. In addition, the 43 kDa peptide was inversely correlated to ER leve ls. This altered ER or related peptide could potentially be a marker o f biologically aggressive breast tumors.