Correlation of Forkhead Box c2 with subtypes and invasive ability of invasive breast cancer

Forkhead Box c2 (FOXC2) is a member of forkhead/winged-helix family of transcription factors. The relationship between FOXC2 and invasive breast cancers, including basal-like breast cancer (BLBC, a subtype of breast cancer), remains to be elucidated. In this study, immunohistochemistry was used to detect the expression of FOXC2 in samples from 103 cases of invasive breast cancers and 15 cases of normal mammary glands. The relationship between FOXC2 and clinical parameters of invasive breast cancers such as patient's age, tumor size, lymph node metastasis, tumor grade, the expression of ER, PR, HER-2 and p53, and Ki-67 labeling index (LI) was evaluated. The expression of FOXC2 was detected in parent MCF7 cells, MCF cells transfected with FOXC2 expression vectors and MDA-MB-435 cells by immunohistochemistry and Western blotting. Transwell assay was used to determine the invasive ability of these cells. The results showed that FOXC2 was strongly expressed in basal epithelial cells in normal mammary glands and weakly expressed or even not expressed in glandular epithelial cells. The majority of invasive breast cancers (71.8%, 74/103) had negative or weak expression of FOXC2. However, FOXC2 was strongly expressed in 60.7% of BLBCs. Moreover, FOXC2 was related with tumor grade, p53 expression, ki-67 LI and lymph nodes metastasis. It was expressed in FOXC2-transfected MCF cells and MDA-MB-435 cells but not in parent MCF cells. Transwell assay revealed that MCF cells transfected with FOXC2 expression vectors were more aggressive than the parent MCF cells, suggesting a positive correlation between FOXC2 and the invasion of breast cancer. It was concluded that there is a significant association between FOXC2 and the metastasis of invasive breast cancer. FOXC2 may be used as a new marker for the diagnosis and prognosis prediction of different subtypes of invasive breast cancers.