Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

Intrauterine microdialysis - a novel approach for the assessment and treatment of endometrial paracrine disorders and endometrial cancer in the human female

P Licht MD, S Ackermann MD, S Lehmeyer, V Russu MD, L Wildt MD

Div Gynaecological Endocrinology & Reproductive Medicine, Dept Onstetrics and Gynecology, University of Erlangen, Erlangen, Germany,

AIMS : To develop an intrauterine microdialysis device (IUMD) that allows the selective application of hormones, cytokines or drugs to the endometrium and to simultaneously assess the paracrine response of tissue in the human female in vivo. METHODS: The IUMD consists of two 5 g balloon catheters connected to each other by means of plasmapheresis tubing (Mw. Cut-off: 2.000.000 Da). The system is transcervically inserted into the uterine cavity and continuously perfused with sterile saline at a flow-rate of 30 ml/min. The recovery rate varies between 100% for small molecules (glucose) and 5% for very large molecules. RESULTS: In this study, we have used the IUMD to simulate the paracrine milieu of an early pregnancy by the application of low concentrations of hCG (500 IU/ml) to the endometrium. hCG caused a profound modulation of endometrial paracrine parameters. IGFBP-1 - a marker protein for decidualisation - was selectively detected in the late secretory phase. The molecule was significantly inhibited by the hCG application (p < 0.01). In addition, several cytokines known to be involved in the regulation of implantation (LIF, M-CSF), vascularisation (VEGF) and tissue remodelling (MMP-9) were differentially regulated by hCG. CONCLUSION : In summary, intrauterine microdialysis may represent a new paradigm in the in vivo assessment of endometrial physiology and pathophysiology. The opportunity to directly monitor the response of the tissue to a given stimulus may be of interest also for diagnosis and treatment of atypical endometrial hyperplasia and cancer.

KEY WORDS: microdialysis, endometrium, endometrial cancer, hCG, cytokines.

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on novel therapies.