Coexpression of EphB4 and ephrinB2 in tumor advancement of uterine cervical cancers.
OBJECTIVE
Receptor EphB4 and the corresponding ligand ephrinB2 contribute to tumor growth in various human tumors. This prompted us to study the expression and localization of EphB4 and ephrinB2 in uterine cervical cancers to analyze the EphB4/ephrinB2 functions against clinical backgrounds.


METHODS
Immunohistochemistry and real-time RT-PCR have been done to determine the histoscores and mRNA levels of EphB4 and ephrinB2, respectively, in sixty-two uterine cervical cancer tissue samples. Patient prognoses were analyzed with a 36-month survival rate.


RESULTS
The localization of EphB4 and ephrinB2 was dominantly in the cancer cells of uterine cervical cancers of all cases given. Both the histoscores and mRNA levels of EphB4 and ephrinB2 significantly increased with clinical stages (I<II<III+IV, p<0.001) in uterine cervical cancers. The tumor sizes significantly correlated with the histoscore and mRNA levels of EphB4 and ephrinB2. There were significant differences in histoscores and mRNA levels of EphB4 and ephrinB2 in accordance with lymph node metastasis, but not according to histopathological types. The 36-month survival rates of the 31 patients with high EphB4 and ephrinB2 expression were poor (31% and 19%, respectively), while survival rates for the other 31 patients with low EphB4 and ephrinB2 expression were significantly higher (72% and 73%, respectively).


CONCLUSIONS
Coexpression of EphB4 and ephrinB2 increased with the disease advancement based on clinical stage, lymph node metastasis, tumor size and with poor patient prognoses. Therefore, EphB4/ephrinB2 expression might work on tumor advancement and coexpression of the Eph/ephrin system may potentiate tumor progression leading to poor survival, thus can be recognized as a novel prognostic indicator in the primary tumors of uterine cervical cancers.
Department of Obstetrics and Gynecology, Gifu University School of Medicine, Yanagido 1-1, Gifu City 501-1194, Japan.
Syed Mahfuzul
SM
Alam
Jiro
J
Fujimoto
Israt
I
Jahan
Eriko
E
Sato
Teruhiko
T
Tamaya
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D017931:DNA Primers; D036388:Ephrin-B2 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000235:genetics; D008875:Middle Aged; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D036224:Receptor, EphB4 / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology
D017931:DNA Primers; D036388:Ephrin-B2; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D036224:Receptor, EphB4