Expression and prognostic significance of EFNB2 and EphB4 genes in patients with oesophageal squamous cell carcinoma.
OBJECTIVE
Tyrosine kinases and its receptors play important roles in growth, migration, and invasion of malignant cells. Among those, there are only few reports examining the expression pattern of Eph/ephrin signalling system in oesophageal carcinoma. The prognostic importance of ephrin-B2 ligand (EFNB2) and its receptor EphB4, and its correlation with clinicopathologic characteristics are yet to be delineated in patients with oesophageal carcinoma.


METHODS
EFNB2 gene and EphB4 receptor gene were examined of mRNA specimens in 61 patients with oesophageal squamous cell carcinoma using reverse-transcriptase polymerase chain reaction. EFNB2 protein was selectively examined using an immunohistochemical analysis.


RESULTS
EFNB2 mRNA expression was detected in 38 (62.3%) and EphB4 expression was found in 44 (72.1%) out of 61 cancer tissues analysed. There was a statistically significant correlation between EFNB2 expression and number of lymph node metastasis (P<0.05), and a trend toward statistical significance for correlation between EFNB2 expression and American Joint Committee on Cancer Classification Stage (P<0.1), indicating that EFNB2 expression was up-regulated by advancement of the disease process. EFNB2 protein was strongly expressed in tumour with high mRNA EFNB2 expression and was weakly expressed in tumour with low mRNA expression in some representative tumours. The 5-year overall survival rate (23%) of patients with positive EFNB2 gene expression was significantly worse than 55% of negative expression (P<0.05). The results of multivariate analysis of prognosticators for survival showed that positive EFNB2 gene expression (P<0.01) and number of lymph node metastasis (P<0.05) were identified as significant factors indicative of a poorer survival.


CONCLUSIONS
EFNB2 gene expression may be a biological marker and a useful prognostic indicator in patients with oesophageal squamous cell carcinoma.
Tachibana
M
M
Digestive and General Surgery, Department of Surgery, Faculty of Medicine, Shimane University, Izumo 693-8501, Shimane, Japan. nigeka35@med.shimane-u.ac.jp
Tonomoto
Y
Y
Hyakudomi
R
R
Hyakudomi
M
M
Hattori
S
S
Ueda
S
S
Kinugasa
S
S
Yoshimura
H
H
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D036388:Ephrin-B2 / Q000096:biosynthesis / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012334:RNA, Neoplasm / Q000235:genetics*; D036224:Receptor, EphB4 / Q000096:biosynthesis / Q000235:genetics*; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate / Q000639:trends
D014408:Biomarkers, Tumor; D036388:Ephrin-B2; D012334:RNA, Neoplasm; D036224:Receptor, EphB4