Variation of ER status between primary and metastatic breast cancer and relationship to p53 expression

Objective: Estrogen-dependent growth of breast cancer can be blocked by ant i-estrogens. Estrogen receptor (ER) presence in breast cancer implies respo nsiveness to endocrine therapy. However, for those patients who ultimately develop resistance to endocrine therapy, the mechanisms remain unclear. The present study attempted to compare the expression status of ER mRNA in a s eries of primary breast tumors with matched metastases and explored the rel ation between ER and mutant p53 expression. Methods: In situ hybridization using a digoxigenin-labeled estrogen receptor cDNA probe was employed to de termine the expression of ER mRNA in 52 cases of primary tumors and their m atched axillary lymph node metastases. Immunohistochemical staining using a monoclonal antibody against ER was also performed. Results: ER expression was observed in 53.8% (28/52) of primary tumors and 48% (25/52) of metastas es, while 57.7% (30/52) of primary tumors and 53.8% (28/52) of metastases s howed ER mRNA positivity. There were variations in ER status between in sit u hybridization and immunohistochemistry measurements and between primary t umors and metastases. Mutant p53 expression was inversely associated with E R-negative, high-grade tumors. Conclusions: In situ hybridization may be a more specific and sensitive method for determination of ER status than immu nohistochemistry. It is possible that the biologic properties of ER change, and these changes may influence tumor response to endocrine therapy. In vi ew of the ER variation, it was suggested that the ER status of metastatic t umors in addition to primary tumors should be taken into consideration in o rder to better determine the benefit of clinical endocrine therapy. (C) 200 1 Elsevier Science Inc. All rights reserved.