Overexpression of ephrinB2 and EphB4 in tumor advancement of uterine endometrial cancers.
BACKGROUND
The ligand ephrinB2 and the corresponding receptor EphB4 contribute to tumor growth in various human tumors. This prompted us to study the expression and localization of ephrinB2 and EphB4 in uterine endometrial cancers to analyze the ephrinB2/EphB4 functions against clinical backgrounds.


METHODS
We carried out immunohistochemistry and real-time RT-PCR to determine the histoscores and messenger RNA (mRNA) levels of ephrinB2 and EphB4, respectively, in 68 uterine endometrial cancers and 16 normal endometrium tissue samples. Patient prognoses were analyzed with a 60-month survival rate.


RESULTS
The localization of ephrinB2 and EphB4 was dominantly in the cancer cells of uterine endometrial cancer of all cases given. EphrinB2 and EphB4 histoscores were highly correlated with ephrinB2 and EphB4 mRNA levels, respectively (r = 0.864 and r = 0.615, P < 0.01). Both the histoscores and mRNA levels of ephrinB2 and EphB4 significantly increased with clinical stages (I < II < III, P < 0.01), dedifferentiation (G(1) < G(2) < G(3), P < 0.01) and myometrial invasion (A < B < C, P < 0.01 for ephrinB2 and P < 0.05 for EphB4) in uterine endometrial cancers. The 60-month survival rates of the 34 patients with high ephrinB2 and EphB4 expression were poor (59% and 62% respectively), while for the other 34 patients with low ephrinB2 and EphB4 expression, they were significantly higher (85% and 82%, respectively).


CONCLUSIONS
EphrinB2 and EphB4 were overexpressed during the tumor advancement as dedifferentiation and myometrial invasion. Therefore, ephrinB2/EphB4 might work on tumor advancement and may be recognized as a novel prognostic indicator for uterine endometrial cancers.
Alam
S M
SM
Department of Obstetrics and Gynecology, Gifu University School of Medicine, Yanagido, Gifu City, Japan.
Fujimoto
J
J
Jahan
I
I
Sato
E
E
Tamaya
T
T
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D002454:Cell Differentiation; D016889:Endometrial Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D036388:Ephrin-B2 / Q000032:analysis* / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D036224:Receptor, EphB4 / Q000032:analysis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D036388:Ephrin-B2; D012333:RNA, Messenger; D036224:Receptor, EphB4