Abstract 32: Heterogeneous expression of Her2, estrogen and progesterone receptors in human breast cancer metastasized to the brain

Assessment of hormone (estrogen (ER) and progesterone (PR)) and human epidermal growth factor-2 (Her2) receptors expression in breast cancer has been an accepted standard to predict clinical outcome. Importantly, expression of these receptors in primary breast cancer has been an important predictor of visceral organ metastasis. Although many studies of breast cancer have reported risk factors for brain metastasis, including Her2 positivity and ER negativity, currently it is not possible to accurately predict brain metastasis. One possible reason for this impasse could be the expression of the above receptors in different combinations influencing metastasis to the brain (brain mets). To address this possibility, we analyzed six different human brain mets for the expression of Her-2, ER and PR by the fluorescent in situ hybridization (FISH) and immunohistochemistry procedures. To further validate this data, eight different human primary breast tumors were similarly analyzed. The immunohistochemistry analysis showed that brain mets are heterogenous in the expression of these receptors: five were Her2 positive and one negative; four were ER positive and two were negative; five were PR positive and one negative. However, expression of these receptors in their combination is also heterogenous: three brain mets were positive for all of the Her2, ER and PR; one for Her2 positive but negative for ER/PR; one positive for PR but negative for Her2/ER. Similar heterogenous expression of these receptors in primary tumors were also observed using immunohistochemistry procedure. While this data is mostly corroborative to the FISH analysis, the FISH identified receptor positivity could not be established by immunohistochemistry. Additionally, tumors characterized by immunohistochemistry as PR negative were found to express this receptor, albeit in tens of cells among thousands in brain mets. Such differences in results using these two procedures were noted in the Her2 expression in both brain mets and primary tumors. Undoubtedly, FISH is highly sensitive and identifies gene amplification, whereas, immunohistochemistry allows the detection of receptor expression which is heavily dependent on several factors including accessibility of antigen and affinity of the antibody. In conclusion, our analysis suggests that the currently utilized Her2, estrogen and progesterone receptor detection to predict brain mets needs further refinement to allow for better understanding of the me