Prognostic and Clinicopathological Value of the Expression of FOXC2 & YKL-40 in Carcinoma of the Breast, an Immunohistochemical Study

Background: Breast cancer is considered the commonest and the most fatal female cancer worldwide. There is to an urgent need for discovering recent therapies to identify patient prognosis and improve treatment strategies. Fork-head Box C2 (FOXC2) is a transcription factor which is a key regulator of cancer stem cells (CSC) properties and epithelial mesenchymal transition (EMT) e.g. cancer initiation, metastatic capacity, and resistance to chemotherapy. FOXC2 roles in CSCs properties and EMT regulation in breast cancer needs detailed studies. YKL-40 is known as chitinase-3-like-1 belongs to a family of mammalian proteins that have an amino acid sequence which is similar to the 18-glycosyl hydrolase bacterial chitinases group. Recent studies have found aberrant YKL-40 elevated expression in cancer of various organs, so it may be used as a recent prognostic biomarker for patients with breast cancer. Former researchers have assessed the expression of FOXC2 & YKL-40 separately in cancer patients and relations to prognosis of patients; however, no studies assessed them together in breast cancer patients and the previous results were inconclusive. Accordingly, our study aimed at evaluation of immunohistochemical expressions of FOXC2 & YKL-40 in carcinoma of the breast in a trial to clarify the relation among their expressions, clinicopathological parameters and recurrence of the disease after successive therapy and patients’ prognosis. Methods: we have evaluated expressions of FOXC2 & YKL-40 in sections from 50 paraffin blocks of carcinoma of the breast using immunohistochemistry. We followed up our patients for 3 years for assessment of recurrence of the disease after successive therapy and survival rates. We analyzed the relationship between their combined expression clinicopathological and prognostic parameters. Results: high FOXC2 expression was associated with older age of the patient (p = 0.002), negative ER (p = 0.009), & PR (p = 0.008), positive HER2neu (p = 0.02), aggressive molecular subtype, higher grade of the tumor (p = 0.03), high incidence of distant metastasis (p = 0.011), high incidence of lymph node metastasis, higher KI labeling index, advanced stage, (p < 0.001). high YKL-40 expression was positively correlated with older age of the patient (p = 0.002), negative ER (p = 0.03), & PR (p = 0.04), positive HER2neu (p = 0.02), higher grade of the tumor (p = 0.003), high incidence of distant metastasis (p = 0.04), higher KI labeling index, aggressive molecular subtype, advanced stage, high incidence of lymph node metastasis (p < 0.001). We have found that patients with FOXC2 and YKL-40 overexpression have higher incidence of recurrence of the disease after therapy, poor RFS& OS rates (p < 0.001). Conclusion: Higher expression levels of FOXC2 & YKL-40 are markers of poor prognosis in breast cancer.