Nuclear translocation of HER‐4/c‐erbB‐4 is significantly correlated with prognosis of esophageal squamous cell carcinoma

Abstract

BACKGROUND: HER family is an attractive target for the treatment of esophageal cancer. The clinical relevance of HER-4 has not been yet characterized. METHODS: The expression of HER-4 was immunohistochemically examined in 61 surgically resected esophageal squamous cell carcinomas (ESCC), and the prognostic significance of HER-4 in ESCC was evaluated. RESULTS: HER-4 was positive in the cytoplasm and cell membrane of 51 (84%) tumors, with variable intensity and a heterogeneous distribution, with preferential expression in well or moderately differentiated tumors. Nuclear staining of HER-4 was observed in 37 (61%) cases as well. The membranous/cytoplasmic, but not nuclear, expression of HER-4 was positively correlated with the expression of HER-2 and HER-3. Survival of the HER-4-positive group was significantly better than that of the HER-4-negative group (P < 0.05). Multivariate analysis revealed that extranuclear expression of HER-4 was independently correlated with increased survival. In contrast, nuclear staining of HER-4 was correlated with increased T stage, which resulted in a significant reduction in survival in the HER-4 positive group (P < 0.05). CONCLUSION: Extranuclear HER-4 may have negative effects on the progression of ESCC, whereas nuclear translocation of HER-4 may elicit a tumor-promoting property. Immunohistochemical detection of HER-4 localization is clinically useful to predict the survival of the patients with ESCC.