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Angiogenesis of Uterine Cervical Carcinoma: Characterization by Pharmacokinetic Magnetic Resonance Parameters and Histological Microvessel Density with Correlation to Lymphatic Involvement

Department of Radiological Diagnostics, German Cancer Research Center, D-69120 Heidelberg [H. H., M. V. K., I. Z., A. K., G. B., S. O. S., M. E., G. v. K.], and the Department of Obstetrics and Gynecology [P. G. K., W. W., U. S., C. W.] and the Institute of Physiology and Pathophysiology [P. V.], University of Mainz, D-55101 Mainz, Germany

Dynamic studies of Gd-based contrast agents in magnetic resonance imaging (MRI) are increasingly being used for tumor characterization as well as therapy response monitoring. Because detailed knowledge regarding the pathophysiological properties, which in turn are responsible for differences in contrast enhancement, remains fairly undetermined, it was the aim of this project to: (a) examine the relationship between contrast-enhanced dynamic MRI-derived characteristics and histological microvessel density counts, a recognized surrogate of tumor angiogenesis, from primary or recurrent cancers of the uterine cervix; and (b) correlate these parameters with lymphatic involvement to characterize tumor aggressiveness in terms of lymphatic spread.

Pharmacokinetic parameters (amplitude, A; exchange rate constant, k₂₁) were calculated from a contrast-enhanced dynamic MRI series in 55 patients (ages 25–72 years; mean, 50 years) with biopsy-proven primary (n = 42) or recurrent (n = 13) uterine cervical cancer. Both pharmacokinetic parameters were correlated to histologically determined microvessel density counts (factor VIII-related antigen) and other pathological tumor characteristics obtained from the operative specimens after radical surgery. In addition, the magnetic resonance and histological data were correlated to the presence or absence of lymphatic system involvement.

Pharmacokinetic MRI-derived parameters (A and k₂₁) increased with increasing histological microvessel density counts with r = 0.41 and 0.50, respectively. Lymphatic involvement was more comprehensibly assessed by the pharmacokinetic parameter k₂₁ compared with histological microvessel density, resulting in a higher sensitivity, overall accuracy, and comparable specificity. Contrast-enhanced MRI parameters might prove to be applicable for estimation of tumor angiogenesis in uterine cervical cancer; thus, MRI may become an additional tool to characterize malignant progression in terms of lymphatic involvement in uterine cervical cancer.

¹ To whom requests for reprints should be addressed, at Department of Radiological Diagnostics and Therapy, German Cancer Research Center (DKFZ). Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. Phone: 49-6221-422525; Fax: 49-6221-422531.

Received 3/24/97. Accepted 8/22/97.

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