Original contributions Prognostic significance of microvessel density and vascular endothelial growth factor expression in sinonasal carcinomas B Guido Valente MD a, * , Carlo Mamo MD c , Antonella Bena MD c , Elisa Prudente BTechn a , Cristina Cavaliere BSc d , Simonetta Kerim MD d , Giuseppina Nicotra BSc b , Alberto Comino MD e , Giorgio Palestro MD d , Ciro Isidoro MD b , Fabio Beatrice MD f a Pathology Section, Department of Medical Sciences, Amedeo Avogadro University Medical School, I 28100 Novara, Italy b Laboratory of Molecular Pathology, Department of Medical Sciences, Amedeo Avogadro University Medical School, I 28100 Novara, Italy c Epidemiology Unit, Agenzia Regionale Protezione Ambientale, I 10095 Grugliasco, Italy d Department of Biomedical Sciences and Human Oncology, School of Medicine and San Giovanni Hospital, I 10100 Torino, Italy e Laboratory of Anatomic Pathology, Santa Croce and Carle Hospital, I 12100 Cuneo, Italy f Department of Otolaryngology, Giovanni Bosco Hospital, I 10100 Torino, Italy Received 9 August 2005; revised 18 November 2005; accepted 21 November 2005 Summary The prognostic significance of microvessel density and proliferative activity of the neoplastic cells, evaluated respectively by CD31 and Ki-67 positivity, and immunohistochemical expression of vascular endothelial growth factor (VEGF) was retrospectively investigated in 105 cases of sinonasal carcinoma (80 surgical specimens and 25 biopsies). The most represented histologic types were intestinal-type adenocarcinoma found in 36 patients (34.3%), squamous cell carcinoma (SCC) in 34 (32.4%), mucinous adenocarcinoma (mainly made up of signet-ring cell patterns) in 15 (14.3%), and adenoid cystic carcinoma in 7 (6.7%). Microvessel density values (in vessels per square millimeter), VEGF, and Ki-67 were not dependent on histologic type but were rather correlated to the histologic grading in SCC. Clinical data were available for 92 (87.6%) of 105 patients, with minimum follow-up of 48 months. Most of the patients (81.5%) were at an advanced stage (T3-T4) at diagnosis. The values of all markers were correlated to tumor stage ( P = .03). Multivariate analysis showed that both microvessel density and proliferative activity of the neoplastic cells were independent prognostic parameters (mortality hazard ratio, 1.33 and 1.60, respectively). Although VEGF expression was not correlated to prognosis on the whole series ( P = .06), it was a powerful prognostic marker when the analysis was restricted to the group of SCCs (hazard ratio, 3.02; 90% confidence interval, 1.58-5.80). These results show that tumor neoangiogenesis, expressed by microvessel density, together with proliferative activity, is a pathologic marker with a strong prognostic impact in sinonasal carcinomas. Therefore, it may be a 0046-8177/$ – see front matter D 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.humpath.2005.11.021 B This work was supported by a grant from the Piedmont Region. * Corresponding author. E-mail address: guido.valente@med.unipmn.it (G. Valente). Keywords: Sinonasal carcinoma; Microvessel density; Tumor angiogenesis Human Pathology (2006) 37, 391 – 400 www.elsevier.com/locate/humpath