Protein expression of HER2, 3, 4 in gastric cancer: correlation with clinical features and survival.
OBJECTIVE
Despite significant improvements in targeted therapies for patients with advanced gastric cancer (GC), the prognosis of those patients remains poor. This study explores the expression and clinicopathological significance of human epidermal growth factor receptor 2, 3 and 4 (HER2, HER3, HER4) in GC, in order to find more prognostic biomarkers of GC and putative targets of therapy.


METHODS
Immunohistochemistry was performed for HER2, HER3 and HER4 in 498 patients with GC using tissue microarray. Correlations between the receptor expression and clinicopathological features, as well as prognosis of the patients were statistically analysed.


RESULTS
The high expression rates of HER2, HER3 and HER4 proteins in the patients were 8.6% (43/498), 20.7% (103/498) and 13.3% (66/498), respectively. High expression of HER2 and HER3 was correlated with proximal GC of the cardia (p<0.05). High expression of HER3 was associated with the tumour depth, tumour node metastasis (TNM) stage and lymph node metastasis (p<0.05). High expression of HER4 was associated with TNM stage (p<0.05) only. According to a regression model, high expression of HER3 was significantly associated with patients' poor survival (p=0.004). High expression rates of HER2, HER3 and HER4 were correlated with each other, but they were all associated merely with histologically intestinal-type adenocarcinoma of GC (p<0.05).


CONCLUSIONS
HER3 is correlated with the malignant biological behaviour of GC. Expression of HER3 is a significant predictor of poor survival in GC. Therefore, the development of HER3-targeted agents may provide new possibilities in the treatment of GC.
Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Xiao Xiao
XX
He
Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Li
L
Ding
Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Yuan
Y
Lin
Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Man
M
Shu
Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Jian Ming
JM
Wen
Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Ling
L
Xue
D000230:Adenocarcinoma / Q000737:chemistry* / Q000401:mortality / Q000556:secondary / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D005743:Gastrectomy; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D020893:Receptor, ErbB-3 / Q000032:analysis*; D066247:Receptor, ErbB-4 / Q000032:analysis*; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D055815:Young Adult
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4; C508053:ERBB2 protein, human; C581292:ERBB3 protein, human; C587689:ERBB4 protein, human
CANCER RESEARCH; GASTRIC CANCER; IMMUNOHISTOCHEMISTRY