High expression of HER3 is associated with a decreased survival in gastric cancer.
BACKGROUND
The role of human epidermal growth factor receptor (HER) 3 and HER4 has been elucidated in gastric cancer. HER1 and HER2 overexpression are regarded as prognostic factors and targets of treatment. The dimerization of the HER family receptors activates downstream signal pathways and promotes tumor progression. This study investigated the positive correlation between HER1 and HER4 expression and the prognosis of patients with gastric cancers.


METHODS
Tumor samples were obtained from gastric adenocarcinomas of 134 patients who underwent a gastrectomy from 1999 to 2002. The expression of each HER was analyzed in the tumor by immunohistochemical staining. Parametric correlations were done between HER expression and the clinicopathologic findings. A multivariate analysis was done with the overall survival.


RESULTS
HER3 expression was significantly associated with parameters involved with tumor progression, including the depth of tumor invasion (T1 versus T2-T4; P = 0.000), involved lymph nodes (P = 0.000), distant metastasis (P = 0.008), tumor stage (P = 0.000), and recurrent disease (P = 0.000). HER1 was also significantly associated with those factors excluding distant metastasis. A significant relationship was observed between the expression of HER1 and HER3 (P = 0.000). HER3 overexpression was associated with a significantly worse survival (P = 0.0000) and was an independent prognostic factor in the multivariate analysis (hazard ratio, 2.382; 95% confidence interval, 1.009-5.625; P = 0.048).


CONCLUSIONS
HER3 overexpression is strongly associated with tumor progression and poor prognosis of patients with gastric cancer. It may become a new prognostic factor and a target of treatment.
Hayashi
Mikiko
M
Department of Surgical Oncology, Tokyo Medical and Dental University, Tokyo, Japan.
Inokuchi
Mikito
M
Takagi
Yoko
Y
Yamada
Hiroyuki
H
Kojima
Kazuyuki
K
Kumagai
Jiro
J
Kawano
Tatsuyuki
T
Sugihara
Kenichi
K
D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D020893:Receptor, ErbB-3 / Q000096:biosynthesis*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*
D020893:Receptor, ErbB-3