Heterogeneity in the expression of receptors in the human breast cancer metastasized to the brain

Assessment of the human epidermal growth factor receptor-2 (Her2/ErbB2) and estrogen receptor (ER) and progesterone receptor (PR) expression in breast cancer has been an accepted standard to predict clinical outcome. Expression of these receptors in primary breast cancer has also been an important predictor of visceral organ metastasis. Many studies of breast cancer have reported risk factors for brain metastasis that include Her2/ErbB2 positivity, ER negativity, and negativity for all the above three receptors. However, it is not clear whether expression of these receptors would persist subsequent to brain metastasis. To address this possibility, we analyzed different breast cancer brain metastases (BCBM) for the expression of Her2/ErbB2, ER, and PR by immunohistochemistry procedure. The results showed that BCBM are heterogeneous in the receptor expression: Five BCBMs were Her2/ErbB2-positive and one negative; four BCBMs were ER-positive, and two were negative; five BCBMs were PR-positive and one negative. However, expression of these receptors in their combination is also heterogeneous: Four BCBMs were positive for all of the Her2/ErbB2, ER, and PR; one BCBM was positive for Her2/ErbB2 and PR but negative for ER; one BCBM was positive for PR but negative for Her2/ErbB2/ER. Similar heterogeneity in the expression of these receptors was also observed in primary tumors. Importantly, BCBM tumors that were assigned as ER- and PR-positive contained tumor cells that lacked expression of these receptors in other regions of the biopsies. Taken together, our findings indicate that the BCBM exhibit heterogeneity in the expression amounts of Her2/ErbB2, ER, and PR, which could be a result of the influence of tumor microenvironment in the brain or different tumor cells populating the metastatic region.