FOXA1 and CK7 expression in esophageal squamous cell carcinoma and its prognostic significance

Ying Xu,  Wei Wang, Lei Li, Jianli Liu, Xiaoxiao Wu, Juan Yu, Hongbo Wang,  Wen Cui,  Renya Zhang

Abstract:

Esophageal Squamous Cell Carcinoma (ESCC) is one of the most common malignant tumors in human. Some ESCC cells express adenocarcinoma cell markers, such as Cytokeratin 7 (CK7), but the clinical significance of these cells in ESCC is unknown. Immunohistochemical analysis of CK7 and Fork head box protein A1(FOXA1, an upstream regulator of CK7) was performed on 610 ESCC specimens using tissue microarray. In total, positive staining of CK7 was 59/594 (10%). CK7 expression was correlated with ESCC differentiation (P=0.006). The expression of CK7 is associated with poor overall survival (OS) of ESCC patients (P=0.0498). FOXA1 positive staining was 180/586(31%). FOXA1 expression correlates with differentiation (P<0.0001) and vascular invasion status (P=0.016) of ESCC. FOXA1 expression was non-independently correlated with poor prognosis of OS in ESCC patients (P=0.1198), but correlated with the prognosis of ESCC patients in some specific pathological characteristics, such as age less than 61 years (P=0.0066), tumor located in the middle segment of esophagus (P=0.0046), and non-lymph node metastasis (P=0.0377). Correlation analysis between the CK7 and FOXA1 expression was positive (P<0.0001). In conclusion, FOXA1 expression was positive correlated with CK7 expression. CK7 expression is an independent prognostic factor for ESCC, and FOXA1 is a non-independent prognostic factor. CK7 and its upstream factor FOXA1 both can be used as potential targets for ESCC therapy.