ANGIOGENIC ACTIVITY OF CERVICAL-CARCINOMA - ASSESSMENT BY FUNCTIONAL MAGNETIC-RESONANCE IMAGING-BASED PARAMETERS AND A HISTOMORPHOLOGICAL APPROACH IN CORRELATION WITH DISEASE OUTCOME

Angiogenesis plays a fundamental role in tumor growth and metastasis, What is needed is a quantitative, noninvasive, and repeatable assay to estimate functional angiogenic activity of the entire tumor. The aims of the present study were to: (a) examine the relationship between fu nctional magnetic resonance imaging (MRI)-based parameters with establ ished histomorphological markers of tumor angiogenesis [histological m icrovessel density (HMVD) and vascular endothelial growth factor expre ssion (VEGF)]; and (b) determine the ultimate value of both approaches to assess functional angiogenic active hotspots as markers of disease outcome in patients with cancer of the uterine cervix, Pharmacokineti c parameters (amplitude A, tissue exchange rate constant k(21)) were c alculated from contrast-enhanced dynamic MRI series in 57 patients (me an age, 49 +/- 14 years) with biopsy proven uterine cervical cancer, B oth pharmacokinetic parameters were correlated to histomorphologically determined areas of high HMVD and VEGF expression obtained from the o perative specimens after radical surgery. In addition, the functional MRI and histomorphological data were used to assess disease outcome. A significant association was found between HMVD and the amplitude A (P < 0.001) and a less pronounced association with k(21), (P < 0.05), re spectively. No significant associations were found between the pharmac okinetic parameters (A, k(21)) and VEGF expression. When stratified in to high and low median k(21) groups, median k(21) values >5.4 min(-1) were the only significant (P < 0.05) factors in predicting poor patien t survival. None of the histomorphological markers of angiogenesis (HM VD or VEGF expression) showed any predictive power;We have found that: (a) focal hotspots of HMVD are the pathophysiological basis for diffe rences in functional MRI; (b) areas of high microvessel density and mi crovessel permeability do not necessarily coincide, as demonstrated by the histomorphological and functional MRI findings; (c) the functiona l angiogenic activity of a tumor may not be sufficiently characterized by a histomorphological approach but rather by a functional MRI-based approach; and (d) functional MRT-based analysis may assess tumor angi ogenic activity in terms of disease outcome more comprehensively than the histomorphological approach.