Clinical Cancer Research, Vol 4, Issue 10 2305-2312, Copyright © 1998 by American Association for Cancer Research

ARTICLES

Angiogenic activity of cervical carcinoma: assessment by functional magnetic resonance imaging-based parameters and a histomorphological approach in correlation with disease outcome

H Hawighorst, W Weikel, PG Knapstein, MV Knopp, I Zuna, SO Schonberg, P Vaupel and G van Kaick
Department of Radiological Diagnostics, German Cancer Research Center, Heidelberg. H.Hawighorst@dkfz-heidelberg.de

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 functional magnetic resonance imaging (MRI)-based parameters with established histomorphological markers of tumor angiogenesis [histological microvessel density (HMVD) and vascular endothelial growth factor expression (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. Pharmacokinetic parameters (amplitude A, tissue exchange rate constant k21) were calculated from contrast-enhanced dynamic MRI series in 57 patients (mean age, 49 +/- 14 years) with biopsy proven uterine cervical cancer. Both pharmacokinetic parameters were correlated to histomorphologically determined areas of high HMVD and VEGF expression obtained from the operative 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 k21, (P < 0.05), respectively. No significant associations were found between the pharmacokinetic parameters (A, k21) and VEGF expression. When stratified into high and low median k21 groups, median k21 values >5.4 min(-1) were the only significant (P < 0.05) factors in predicting poor patient survival. None of the histomorphological markers of angiogenesis (HMVD or VEGF expression) showed any predictive power. We have found that: (a) focal hotspots of HMVD are the pathophysiological basis for differences in functional MRI; (b) areas of high microvessel density and microvessel permeability do not necessarily coincide, as demonstrated by the histomorphological and functional MRI findings; (c) the functional 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 MRI-based analysis may assess tumor angiogenic activity in terms of disease outcome more comprehensively than the histomorphological approach.

This article has been cited by other articles:

				Y. Zou, M. Zhang, Q. Wang, D. Shang, L. Wang, and G. Yu Quantitative Investigation of Solitary Pulmonary Nodules: Dynamic Contrast-Enhanced MRI and Histopathologic Analysis Am. J. Roentgenol., July 1, 2008; 191(1): 252 - 259. [Abstract] [Full Text] [PDF]

				J. Hillengass, K. Wasser, S. Delorme, F. Kiessling, C. Zechmann, A. Benner, H.-U. Kauczor, A. D. Ho, H. Goldschmidt, and T. M. Moehler Lumbar Bone Marrow Microcirculation Measurements from Dynamic Contrast-Enhanced Magnetic Resonance Imaging Is a Predictor of Event-Free Survival in Progressive Multiple Myeloma Clin. Cancer Res., January 15, 2007; 13(2): 475 - 481. [Abstract] [Full Text] [PDF]

				M. A. Rosen and M. D. Schnall Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Assessing Tumor Vascularity and Vascular Effects of Targeted Therapies in Renal Cell Carcinoma Clin. Cancer Res., January 15, 2007; 13(2): 770s - 776s. [Abstract] [Full Text] [PDF]

				M. Atri New Technologies and Directed Agents for Applications of Cancer Imaging J. Clin. Oncol., July 10, 2006; 24(20): 3299 - 3308. [Abstract] [Full Text] [PDF]

				A. S. Doria, M. Noseworthy, W. Oakden, R. Moineddin, T. Rayner, V. Tassos, D. Engelberts, K. Pritzker, M. Rogers, R. Jong, et al. Dynamic contrast-enhanced MRI quantification of synovium microcirculation in experimental arthritis. Am. J. Roentgenol., April 1, 2006; 186(4): 1165 - 1171. [Abstract] [Full Text] [PDF]

				Y. Cao, P. C. Sundgren, C. I. Tsien, T. T. Chenevert, and L. Junck Physiologic and Metabolic Magnetic Resonance Imaging in Gliomas J. Clin. Oncol., March 10, 2006; 24(8): 1228 - 1235. [Abstract] [Full Text] [PDF]

				H. W. M. van Laarhoven, L.-F. de Geus-Oei, B. Wiering, J. Lok, M. Rijpkema, J. H. A. M. Kaanders, P. F. M. Krabbe, T. Ruers, C. J. A. Punt, A. J. van der Kogel, et al. Gadopentetate Dimeglumine and FDG Uptake in Liver Metastases of Colorectal Carcinoma as Determined with MR Imaging and PET Radiology, October 1, 2005; 237(1): 181 - 188. [Abstract] [Full Text] [PDF]

				S. Rehman and G. C. Jayson Molecular Imaging of Antiangiogenic Agents Oncologist, February 1, 2005; 10(2): 92 - 103. [Abstract] [Full Text] [PDF]

				B. F. Jordan, M. Runquist, N. Raghunand, R. J. Gillies, W. R. Tate, G. Powis, and A. F. Baker The Thioredoxin-1 Inhibitor 1-Methylpropyl 2-Imidazolyl Disulfide (PX-12) Decreases Vascular Permeability in Tumor Xenografts Monitored by Dynamic Contrast Enhanced Magnetic Resonance Imaging Clin. Cancer Res., January 15, 2005; 11(2): 529 - 536. [Abstract] [Full Text] [PDF]

				A R Padhani MRI for assessing antivascular cancer treatments Br. J. Radiol., December 1, 2003; 76(suppl_1): S60 - S80. [Abstract] [Full Text] [PDF]

				B. Morgan, A. L. Thomas, J. Drevs, J. Hennig, M. Buchert, A. Jivan, M. A. Horsfield, K. Mross, H. A. Ball, L. Lee, et al. Dynamic Contrast-Enhanced Magnetic Resonance Imaging As a Biomarker for the Pharmacological Response of PTK787/ZK 222584, an Inhibitor of the Vascular Endothelial Growth Factor Receptor Tyrosine Kinases, in Patients With Advanced Colorectal Cancer and Liver Metastases: Results From Two Phase I Studies J. Clin. Oncol., November 1, 2003; 21(21): 3955 - 3964. [Abstract] [Full Text] [PDF]

				C. Bremer, M. Mustafa, A. Bogdanov Jr, V. Ntziachristos, A. Petrovsky, and R. Weissleder Steady-State Blood Volume Measurements in Experimental Tumors with Different Angiogenic Burdens--A Study in Mice Radiology, January 1, 2003; 226(1): 214 - 220. [Abstract] [Full Text] [PDF]

				J. M. Provenzale, G. R. Wang, T. Brenner, J. R. Petrella, and A. G. Sorensen Comparison of Permeability in High-Grade and Low-Grade Brain Tumors Using Dynamic Susceptibility Contrast MR Imaging Am. J. Roentgenol., March 1, 2002; 178(3): 711 - 716. [Abstract] [Full Text] [PDF]