Estrogen receptor alpha is a novel marker expressed by follicular dendritic cells in lymph nodes and tumor-associated lymphoid infiltrates.

During routine assessment of the hormonal phenotype of breast carcinomas, we detected expression of the estrogen receptor (ER) in the germinal centers of reactive lymphoid follicles surrounding malignant foci. To confirm and extend this finding, we compared ER-alpha, progesterone receptor (PR), and androgen receptor (AR) immunostaining in hyperplastic or metastatic lymph nodes obtained from patients with various pathology, disease location, gender and age. Irrespective of these parameters, we found that: 1) ER-alpha-positive cells were located prevalently in germinal centers, 2) the PR was weakly expressed by cells within and surrounding germinal centers, and 3) the androgen receptor was undetectable. Transcripts for ER-alpha and PR were also detected by reverse transcription-polymerase chain reaction on laser-microdissected lymph node germinal centers. Morphologically, the ER-positive cells resemble dendritic cells and by double immunostaining were found to express both CD21 and CD23, which is characteristic of follicular dendritic cells. Finally, we assessed the effects of Tamoxifen treatment by comparing the numbers of ER-positive follicular dendritic cells in lymph nodes obtained from breast cancer patients before and after treatment. The results show that Tamoxifen treatment generated larger germinal centers with more abundant ER(+)/CD21(+)/CD23(+) cells. Taken together, these results open new perspectives on the effects of sex steroids and their antagonists on the human response in cancer and inflammation.