Wide expression of ZEB1 in sarcomatous component of spindle cell carcinoma of the esophagus.

The pathogenesis of sarcomatous component in spindle cell carcinoma (SpCC) of the esophagus is unclear. To investigate the involvement of epithelial-mesenchymal transition (EMT) in sarcomatous differentiation, we performed immunohistochemistry for Slug, Twist, ZEB1, and ZEB2, transcription factors associated with EMT and E-cadherin, in 14 cases of SpCC of the esophagus. In order to verify the neoplastic nature of sarcomatous components, TP53 mutation status and protein expression were examined in each case. Nuclear ZEB1 expression was extensive in the sarcomatous component, greater than invasive front of carcinoma components (P < 0.0001). Membranous E-cadherin expression was mostly lost in sarcomatous cells in all cases (P < 0.0001). The p53 expression pattern was almost concordant between the two areas in all cases. TP53 mutation analysis revealed that seven cases harbored identical mutations in both components. One case had mutations only in the sarcomatous component. It is noteworthy that none of them harbored mutation in exon 5, unlike conventional esophageal squamous cell carcinoma. These findings show that ZEB1 are widely expressed in the sarcomatous area of SpCC of the esophagus, suggesting the involvement of EMT. The avoidance of exon 5 in terms of TP53 mutation may also be a feature of the tumor.