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Nuclear translocation of HER‐4/c‐erbB‐4 is significantly correlated with prognosis of esophageal squamous cell carcinoma
Author(s) -
Xu Shuangta,
Kitayama Joji,
Yamashita Hiroharu,
Souma Daisuke,
Nagawa Hirokazu
Publication year - 2007
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.20892
Subject(s) - immunohistochemistry , medicine , esophageal cancer , pathology , stage (stratigraphy) , carcinoma , staining , clinical significance , cell , cancer , biology , paleontology , genetics
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. J. Surg. Oncol. 2008;97:44–50. © 2007 Wiley‐Liss, Inc.