A combination of GATA3 and SOX10 is useful for the diagnosis of metastatic triple-negative breast cancer.

In metastatic breast cancer (MBC), it can be difficult to establish the origin if the primary tumor is triple negative or if there is a loss of biomarker expression. SOX10 expression has been reported in primary triple-negative breast cancer but is poorly studied in metastatic lesions. In this study, the diagnostic utility of a panel of SOX10, GATA3, and androgen receptor (AR) in MBC negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 was evaluated and compared with the expression of these markers in the matched primary breast cancer. In a series of 57 triple-negative MBCs, 82% were positive for GATA3, 58% for SOX10, and 25% for AR. Nearly all MBCs (95%) were positive for either GATA3 or SOX10, with 46% dual positive and 5% of cases negative for both markers. Most GATA3-negative MBC cases were SOX10 positive (70%). AR expression was only seen in GATA3-positive MBC (25%) and was significantly more frequent in SOX10-negative MBC (48%) versus SOX10-positive MBC (9%; P = .001). Concordance for GATA3, SOX10, and AR between the primary and metastasis was 89%, 88%, and 80%, respectively. Although GATA3 is a more sensitive lineage marker than SOX10 in MBC, SOX10 is a useful adjunct because it is positive in most GATA3-negative breast metastases. Using both GATA3 and SOX10 is recommended for confirming breast as the site of origin in metastases that lack estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression, whereas the addition of AR is not helpful.