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


CONCLUSIONS
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.
Xu
Shuangta
S
Department of Surgical Oncology, The University of Tokyo Graduate School of Medicine, Hongo, Tokyo, Japan.
Kitayama
Joji
J
Yamashita
Hiroharu
H
Souma
Daisuke
D
Nagawa
Hirokazu
H
D021581:Active Transport, Cell Nucleus; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D066246:ErbB Receptors / Q000032:analysis / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D066247:Receptor, ErbB-4
C587689:ERBB4 protein, human; D066246:ErbB Receptors; D066247:Receptor, ErbB-4