Dynamic CT Evaluation of Tumor Vascularity in Renal Cell Carcinoma.

OBJECTIVE The purpose of our study was to evaluate the correlation between the enhancement parameters of dynamic CT; the carcinoma tissue microvessel density (MVD, a hotspot method to provide a histologic assessment of tumor vascularity); and tumor nuclear grade in renal cell carcinomas. SUBJECTS AND METHODS Twenty-four patients with histologically diagnosed renal cell carcinoma underwent dynamic enhanced CT. Enhancement parameters, slope of the time-density curve, the density difference before and after tissue enhancement (deltaH), tissue blood ratio (TBR), and area under the time-density curve (AR), were calculated for all lesions. Pathology slides corresponding to the CT plane were stained using mouse antihuman CD34 monoclonal antibody and H and E. Fuhrman nuclear grade was used. Vascular hot spots of microvessels were recorded. Spearman's rank correlation was performed to determine the strength of the relationship between enhancement parameters, MVD determinations, and tumor nuclear grade. RESULTS MVD with CD34 staining revealed uneven distribution of positively stained vascular endothelial cells in renal cell carcinoma lesions. Heterogeneous distribution of contrast enhancement was seen among and within individual tumors. The tumors appeared as uneven patterns on time-density curves of renal cell carcinoma lesions. Enhancement parameters of H (median, 21.0 H; range, 2.2-105.8 H), TBR (median, 39%; range, 10.7-154.7%), AR (median, 1.58 H x sec; range, 0.23-3.67 H x sec), and slope (median, 2.76; range, 0.53-6.76) varied greatly. Renal cell carcinoma tissue MVD significantly correlated with all enhancement parameters of dynamic CT. The correlation coefficients (r) were 0.62, 0.54, 0.55, and 0.44, respectively, for delta H, slope, TBR, and AR (p < 0.0 5). All enhancement parameters did not significantly correlate with tumor nuclear grade. They were not predictive of nuclear grade. CONCLUSION Enhancement parameters of dynamic CT may be suited to evaluate tumor vascularity in vivo. Dynamic enhanced CT images may reflect the heterogeneity of tumor angiogenesis on the basis of the correlation between enhancement parameters and MVD of renal cell carcinoma.

[1]  V. Sukhatme,et al.  Endostatin: yeast production, mutants, and antitumor effect in renal cell carcinoma. , 1999, Cancer research.

[2]  R. Slutsky,et al.  Tissue distribution and magnetic resonance spin lattice relaxation effects of gadolinium-DTPA. , 1985, Radiology.

[3]  T. Fujioka,et al.  Antitumor effects of angiogenesis inhibitor 0-(chloroacetyl-carbamoyl) fumagillol (TNP-470) against murine renal cell carcinoma. , 1996, The Journal of urology.

[4]  R. Kerbel,et al.  Consequences of angiogenesis for tumor progression, metastasis and cancer therapy. , 1995, Anti-cancer drugs.

[5]  S. Fox,et al.  Quantification of angiogenesis in solid human tumours: an international consensus on the methodology and criteria of evaluation. , 1996, European journal of cancer.

[6]  J. Folkman.  Tumor angiogenesis: therapeutic implications. , 1971, The New England journal of medicine.

[7]  G. Kang,et al.  Multiphase contrast-enhanced CT imaging in hepatocellular carcinoma correlation with immunohistochemical angiogenic activities. , 2007, Academic radiology.

[8]  Y. Ge,et al.  Single-level dynamic spiral CT of hepatocellular carcinoma: correlation between imaging features and density of tumor microvessels. , 2004, World journal of gastroenterology.

[9]  T. D’amico.  Angiogenesis in non-small cell lung cancer. , 2004, Seminars in thoracic and cardiovascular surgery.

[10]  G Brix,et al.  Uterine cervical carcinoma: comparison of standard and pharmacokinetic analysis of time-intensity curves for assessment of tumor angiogenesis and patient survival. , 1998, Cancer research.

[11]  E. Fishman,et al.  Application of CT in the investigation of angiogenesis in oncology. , 2000, Academic radiology.

[12]  S. Brem,et al.  Angiogenesis and blood-brain barrier breakdown modulate CT contrast enhancement: an experimental study in a rabbit brain-tumor model. , 1989, AJR. American journal of roentgenology.

[13]  M D Schnall,et al.  Suspicious breast lesions: MR imaging with radiologic-pathologic correlation. , 1994, Radiology.

[14]  G. Krinsky,et al.  Renal cell carcinoma: Correlation of CT findings with nuclear morphologic grading in 100 tumors , 1994, Abdominal Imaging.

[15]  A R Padhani,et al.  Challenges for imaging angiogenesis. , 2001, The British journal of radiology.

[16]  B. Leibovich,et al.  Contemporary imaging modalities for the surveillance of patients with renal cell carcinoma , 2007, Current urology reports.

[17]  C. Shapiro,et al.  Multi-institutional study of the angiogenesis inhibitor TNP-470 in metastatic renal carcinoma. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  D A Bluemke,et al.  Tumor angiogenesis: tutorial on implications for imaging. , 1997, Radiology.

[19]  N. Weidner.  Intratumor microvessel density as a prognostic factor in cancer. , 1995, The American journal of pathology.

[20]  N. Obuchowski,et al.  Enhancement characteristics of papillary renal neoplasms revealed on triphasic helical CT of the kidneys. , 2002, AJR. American journal of roentgenology.

[21]  D. Connolly,et al.  Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis. , 1989, The Journal of clinical investigation.

[22]  C. Dinney,et al.  The role of angiogenesis in prostate and other urologic cancers: a review. , 2001, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[23]  R. Brasch,et al.  Contrast-enhanced NMR imaging: animal studies using gadolinium-DTPA complex. , 1984, AJR. American journal of roentgenology.

[24]  S. Fuhrman,et al.  Prognostic significance of morphologic parameters in renal cell carcinoma , 1982, The American journal of surgical pathology.

[25]  N. van Bruggen,et al.  Assessing tumor angiogenesis using macromolecular MR imaging contrast media , 1997, Journal of magnetic resonance imaging : JMRI.

[26]  L D Buadu,et al.  Breast lesions: correlation of contrast medium enhancement patterns on MR images with histopathologic findings and tumor angiogenesis. , 1996, Radiology.

[27]  Vicky Goh,et al.  Functional imaging of colorectal cancer angiogenesis. , 2007, The Lancet. Oncology.

[28]  H. Augustin,et al.  Heterogeneity of angiogenesis and blood vessel maturation in human tumors: implications for antiangiogenic tumor therapies. , 2000, Cancer research.

[29]  W E Reddick,et al.  MR imaging of tumor microcirculation: Promise for the new millenium , 1999, Journal of magnetic resonance imaging : JMRI.

[30]  T. Morita,et al.  Antitumour effect of a synthetic analogue of fumagillin on murine renal carcinoma. , 1994, British journal of urology.

[31]  R. M. Hsu,et al.  Small renal cell carcinomas: correlation of size with tumor stage, nuclear grade, and histologic subtype. , 2004, AJR. American journal of roentgenology.

[32]  W. Rathmell,et al.  Renal cell carcinoma , 2007, Current opinion in oncology.

[33]  S. Campbell,et al.  Advances in angiogenesis research: relevance to urological oncology. , 1997, The Journal of urology.

[34]  B R Rosen,et al.  NMR imaging of changes in vascular morphology due to tumor angiogenesis , 1998, Magnetic resonance in medicine.

[35]  N. Weidner,et al.  Tumoural vascularity as a prognostic factor in cancer patients: the evidence continues to grow , 1998, The Journal of pathology.

[36]  R. Jain,et al.  Role of tumor vascular architecture in nutrient and drug delivery: an invasion percolation-based network model. , 1996, Microvascular research.

[37]  W. A. Kaiser,et al.  Dynamic Magnetic Resonance Breast Imaging Using a Double Breast Coil: An Important Step Towards Routine Examination of the Breast , 1990 .