Clinical Significance of 14-3-3 Zeta in Human Esophageal Cancer

Abstract

We recently found 14-3-3 zeta to be overexpressed in esophageal squamous cell carcinomas (ESCCs) by differential display. In the present study we determined the clinical significance of 14-3-3 zeta in esophageal tumorigenesis. Immunohistochemical analysis was carried out in 61 ESCCs, 33 dysplasia samples, 14 hyperplasia samples and 7 matched histologically normal esophageal tissues and correlated with clinicopathological parameters. Cytoplasmic expression of 14-3-3 zeta protein was observed in 95% of ESCCs; 63% of tumors also showed nuclear localization. All hyperplastic and dysplastic tissues distant from ESCCs as well as dysplastic endoscopic biopsies showed cytoplasmic immunopositivity for 14-3-3 zeta, while nuclear localization was observed in 58% of dysplasia and 36% of hyperplasia samples. Matched distant histologically normal epithelia either showed basal cytoplasmic expression of 14-3-3 zeta or no detectable nuclear expression of the protein. Interestingly, immunopositivity observed in normal esophageal tissues and early hyperplasia was confined to cytoplasm only, though significant nuclear expression was detected in dysplasia and ESCC. Immunoblotting and RT-PCR analyses further confirmed 14-3-3 zeta expression in dysplasia and ESCC. To our knowledge, this is the first report demonstrating overexpression of 14-3-3 zeta in esophageal hyperplasia, dysplasia and squamous cell carcinoma, suggesting that alteration in its expression occurs in early stages and is associated with esophageal tumorigenesis.