ORIGINAL ARTICLE VASCULAR FRACTAL DIMENSION AND TOTALVASCULAR AREA IN THE STUDY OF ORAL CANCER Lampros P. Goutzanis, DDS, MD, MSc, PhD, 1 Nikolaos Papadogeorgakis, DDS, MD, MSc, PhD, 1 Petros M. Pavlopoulos, MD, PhD, 2 Vasilis Petsinis, DDS, MD, MSc, PhD, 1 Ioannis Plochoras, MD, 3 Efstathios Eleftheriadis, DDS, MD, PhD, 1 Aikaterini Pantelidaki, MD, 3 Efstratios Patsouris, MD, PhD, 2 Constantinos Alexandridis, DDS, PhD 1 1 Department of Oral and Maxillofacial Surgery, ‘‘Evangelismos’’ General Hospital of Athens, Dental School, University of Athens, Athens, Greece. E-mail: lgoutzan@dent.uoa.gr 2 Department of Pathology, Medical School, University of Athens, Athens, Greece 3 Department of Pathology, ‘‘Evangelismos’’ General Hospital of Athens, Athens, Greece Accepted 17 July 2008 Published online 15 December 2008 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/hed.20959 Abstract: Background. Microvessel quantification has been studied extensively as a factor reflecting angiogenesis in various malignant tumors. The aim of our study was to evaluate the vas- cular fractal dimension and the immunohistochemically positive total vascular area in oral cavity carcinomas in order to assess their potential value as factors reflecting angiogenesis. Methods. Histologic sections from 48 carcinomas and 17 nonmalignant mucosa specimens were evaluated by image analysis using fractal analysis software. Total vascular area was also quantified. Results. Carcinomas presented higher mean values of vas- cular fractal dimension and total vascular area compared to nor- mal mucosa. The difference for the vascular fractal dimension was statistically significant. Conclusions. This study provides evidence that vascular fractal dimension could be used as a reliable factor reflecting angiogenesis in oral squamous cell carcinoma and that there are several statistically significant correlations among total vas- cular area, vascular fractal dimension, nuclear size, and clinico- pathologic factors. V V C 2008 Wiley Periodicals, Inc. Head Neck 31: 298–307, 2009 Keywords: fractal dimension; angiogenesis; oral cancer; total vascular area; image analysis Angiogenesis, the development of new vessels, has a pivotal role in the growth and spread of solid tumors with potential diagnostic and therapeutic applications. 1–3 Tumor angiogenesis is controlled by angiogenic factors directly induced from tumor cells, as well as by factors indirectly induced from surrounding stromal tissues. Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and platelet-derived endothelial growth factor (PDGF) are highly specific for endo- thelium and act as vascular permeability factors. 4 Several studies have shown that neovasculari- zation, as assessed by microvessel counting, con- stitutes a significant prognostic factor in cutane- ous melanoma, 5 breast, 6 prostate, 7 and lung carci- nomas, 8 as well as in head and neck cancer. 9,10 These studies have, however, taken into consider- ation the microvessel density (MVD), overlooking other parameters that might be significant, such as the complexity and the size of microvessels. Fractal geometry is a new development in mathematics, established by Benoit Mandel- brot. 11 It aids the accurate study of the structural Correspondence to: L. P. Goutzanis V V C 2008 Wiley Periodicals, Inc. 298 Vascular Fractal Dimension and Total Vascular Area HEAD & NECK—DOI 10.1002/hed March 2009