Annals of Oncology 14:220-226, 2003
© 2003 European Society for Medical Oncology
Original Paper |
Activation of the receptor protein tyrosine kinase EphB4 in endometrial hyperplasia and endometrial carcinoma
1 Department of Obstetrics and Gynecology, University Hospital, Berne; 2 Institute of Pathology and 3 Department of Clinical Research, University of Berne, Berne, Switzerland
Received 29 May 2002; revised 1 October 2002; accepted 22 October 2002
Background:
Members of the Eph family of tyrosine kinases have been implicated in embryonic pattern formation and vascular development; however, little is known about their role in the adult organism. We have observed estrogen-dependent EphB4 expression in the normal breast suggesting its implication in the hormone-controlled homeostasis of this organ. Since the endometrium is a similarly hormone dependent organ and endometrial carcinoma is thought to result from estrogenic stimulation, we have investigated EphB4 expression in normal human endometrium and during its carcinogenesis.
Patients and methods:
EphB4 expression was analyzed immunohistochemically in 26 normal endometrium specimens, 15 hyperplasias and 102 endometrioid adenocarcinomas and correlated with clinical and prognostic tumor characteristics.
Results:
In normal endometrial tissue no EphB4 protein was detected. Strikingly, we observed a drastic increase (P <0.0001) in the number of EphB4 protein-expressing glandular epithelial cells in the majority of hyperplasias and carcinomas. Moreover, we found a statistically highly significant positive correlation between EphB4 expression and post-menopausal stage of the patient (P = 0.007).
Conclusions:
These findings indicate that in the endometrium, EphB4 is an early indicator of malignant development and, thus, EphB4 may represent a potent tool for diagnosis and therapeutic intervention.
Key words: endometrial cancer, immunohistochemistry, tyrosine kinase
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