Immunohistochemistry of Estrogen and Progesterone Receptors Reconsidered: Experience with 5,993 Breast Cancers

Paraffin sections or fine-needle aspiration smears from 5,993 cases of invasive mammary carcinomas were assessed immunohistochemically for estrogen receptor (ER; 1D5) and progesterone receptor (PR; 636) expression. Staining pattern and intensity were correlated with histologic subtypes and nuclear grades of tumors. Positive nuclear staining for ER and PR was observed in 75% and 55% of invasive carcinomas, respectively. In 92% of ER+ cases, diffuse and uniform staining of most tumor cells was observed. In the remaining 8%, a focal ER reaction was seen, usually because of inadequate fixation. In 21% of PR+ tumors, the reaction was heterogeneous or focal but unrelated to fixation. There were no ER-, PR+ tumors. All pure tubular, colloid, and infiltrating lobular carcinomas were ER+. All medullary, apocrine, and metaplastic and most high-nuclear-grade carcinomas were ER-. With monoclonal antibody 1D5 and antigen retrieval, immunohistochemical reaction for ER in breast cancer usually is an all-or-none phenomenon; therefore, quantitation of results is unnecessary. Despite antigen retrieval, inadequate fixation can cause false-negative results; evaluation of internal positive control samples is imperative. ER positivity and negativity are predictable in certain histologic types and nuclear grades of breast cancer. The reaction for PR can be heterogeneous or focal.