Reduced expression of EphB2 is significantly associated with nodal metastasis in Chinese patients with gastric cancer.
OBJECTIVE
EphB2 is a member of the Eph receptor tyrosine kinase family that has been involved in the regulation of cytoskeleton organization and cell migration in various cell types. Its role and regulation in carcinogenesis is controversial, especially in gastric cancer. We detected EphB2 expression and determined its clinical significance and explored its underlying molecular mechanism in gastric cancers.


METHODS
Tissue microarray blocks containing primary gastric cancer, lymph node metastases, and adjacent normal mucosa specimens obtained from 337 Chinese patients were constructed. Expression of EphB2 in these specimens was analyzed using immunohistochemistry. Mutation analysis at the A9 tract in exon 17 and loss of heterozygosity analysis at the EphB2 gene locus were carried out in 13 sporadic EphB2-negative gastric cancers.


RESULTS
Complete loss of EphB2 expression was observed in 177 (52.5%) of the 337 primary tumor and 41 (82%) of the 50 nodal metastases. Loss of EphB2 expression was significantly associated with advanced T stage, nodal metastasis, advanced disease stage, and poor histological differentiation. Loss of EphB2 expression correlated significantly with poor survival rates in both univariate and multivariate analysis. No frameshift mutation, but a higher frequency of allelic loss, was found in EphB2-negative primary and metastatic tumor samples.


CONCLUSIONS
Frequent deletion and decreased expression of EphB2 protein suggested it as a negative biomarker for gastric carcinogenesis and a potential predictor of the outcome of patients with gastric cancer.
Yu
Guanzhen
G
Department of Medical Oncology, Changzheng Hospital, Hetian Road 64, Shanghai 200070, People's Republic of China.
Gao
Yunshu
Y
Ni
Canrong
C
Chen
Ying
Y
Pan
Jun
J
Wang
Xi
X
Ding
Zhiwei
Z
Wang
Jiejun
J
D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D002681:China; D006801:Humans; D007120:Immunochemistry; D019656:Loss of Heterozygosity; D008207:Lymphatic Metastasis; D036183:Receptor, EphB2 / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology*
D036183:Receptor, EphB2