Few studies have investigated the features of FOXC1 protein expression in invasive breast cancer subtypes as defined by immunohistochemistry (IHC)–based surrogate molecular classification.


To investigate the diagnostic utility of the IHC-based FOXC1 test in breast cancer subtyping and to evaluate the correlation between FOXC1 expression and clinicopathologic parameters in triple-negative breast cancer (TNBC).


FOXC1 expression was evaluated with IHC in a large cohort of 2443 patients with breast cancer. Receiver operating characteristic (ROC) curves were used to assess the diagnostic ability of FOXC1 expression to predict the triple-negative phenotype and to identify the best cutoff value. FOXC1 expression was correlated with the clinicopathologic parameters of TNBC.


The expression rate of FOXC1 in TNBC was significantly higher than in other subtypes. The area under the ROC curve confirmed the high diagnostic value of FOXC1 for the prediction of the triple-negative phenotype. The cutoff value of 1% showed a maximized sum of sensitivity and specificity. In TNBC, FOXC1 expression was significantly associated with aggressive tumor phenotypes. Furthermore, FOXC1 expression was primarily observed in invasive breast carcinoma of no special type and metaplastic carcinoma but rarely in invasive carcinoma with apocrine differentiation. Correspondingly, FOXC1 expression was significantly associated with the expression of basal markers but was negatively correlated with apocrine-related markers in TNBC.


In conclusion, FOXC1 is a highly specific marker for the triple-negative phenotype. Moreover, immunohistochemical detection of FOXC1 expression can be used as an additional diagnostic tool for the triple-negative phenotype and subclassification in TNBC.

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This work was supported in part by a grant from Shanghai Municipal Science and Technology Commission (No.18ZR1407600, WTY) and the National Natural Science Foundation of China (No.82072921, WTY; No. 82002800, ML).

The authors have no relevant financial interest in the products or companies described in this article.

Presented at the virtual United States and Canadian Academy of Pathology's 110th Annual Meeting; March 13–18, 2021.

Data availability: The datasets used and analyzed during this study are available from the corresponding author on reasonable request.

Supplementary data