Please cite this article in press as: Metwaly H, et al. Vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS) in oral lichen planus: An immunohistochemical study for the correlation between vascular and inflammatory reactions. J Oral Maxillofac Surg Med Pathol (2014), http://dx.doi.org/10.1016/j.ajoms.2013.09.009 ARTICLE IN PRESS G Model JOMSMP-226; No. of Pages 7 Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (2014) xxx–xxx Contents lists available at ScienceDirect Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology j o ur nal ho me pa ge: www.elsevier.com/locate/jomsmp Original Research Vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS) in oral lichen planus: An immunohistochemical study for the correlation between vascular and inflammatory reactions Hamdy Metwaly a,b,∗ , Mohamed Abdel-Moniem Ebrahem c , Takashi Saku d a Department of Oral Pathology, Faculty of Dentistry, Tanta University, Tanta, Egypt b Department of Oral & Maxillofacial Surgery and Diagnostic Sciences, College of Dentistry, Qassim University, Saudi Arabia c Department of Oral Medicine, Periodontology and Oral Diagnosis, Faculty of Dentistry, Minia University, Egypt d Division of Oral Pathology, Niigata University Graduate School of Medical and Dental Sciences and Section of Oral Pathology, Department of Surgical Pathology, Niigata University Hospital, Niigata, Japan a r t i c l e i n f o Article history: Received 30 April 2013 Received in revised form 9 August 2013 Accepted 11 September 2013 Available online xxx Keywords: Oral lichen planus Immunohistochemistry VEGF iNOS MVD CD68 a b s t r a c t Objectives: Oral lichen planus (OLP) is characterized by a subepithelial lymphocytic infiltration. To find the correlation between vascular and inflammatory reaction, the expressions of vascular endothelial growth factor (VEGF), inducible nitric oxide synthase (iNOS), CD34, and CD68 were investigated. Materials and methods: 30 cases of OLP and 20 normal oral tissues samples were subjected to immunohis- tochemistry for VEGF, iNOS, CD34 and CD68. CD34-positive (+) blood vessels (microvessel density, MVD), degree of lymphocytic infiltration, and CD68+ macrophages were correlated with the expression of VEGF and iNOS. OLP cases were histopathologically subdivided into active (non erosive and erosive/ulcerative) and non-active stages. Results: Expression of VEGF was observed in all epithelial layers of OLP while iNOS was in basal and parabasal layers. They were significantly higher (P < 0.001) than those in controls. The mean MVD (CD34+) was significantly increased in all cases of OLP (P < 0.05), especially in the active (erosive/ulcerative) stage (P < 0.01) compared with controls. The mean number of CD68+ cells was significantly increased (P < 0.01) in OLP, especially higher in the active (erosive/ulcerative) OLP (P < 0.001). The expressions of VEGF (P < 0.05) and iNOS (P < 0.01) were significantly correlated in OLP. There was significant positive correlations between the lymphocytic infiltration and the expressions of VEGF and iNOS (P < 0.05), MVD (P < 0.01), and CD68 counts (P < 0.001) in OLP. Conclusion: The present results indicated that the upregulation of VEGF and iNOS plays an important role in pathogenesis of OLP through activated angiogenesis and chronic inflammatory cell infiltrates. Novel strategies directed to inhibition of these markers could be developed for OLP treatment. © 2013 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd. All rights reserved.  1. Introduction Oral lichen planus (OLP) is a relatively common chronic inflam- matory autoimmune disease of oral mucosa thought to have a multifactorial origin that involve immunopathogenesis including T cells and macrophages with a prevalence rate of 0.5% and 2.2% of  AsianAOMS: Asian Association of Oral and Maxillofacial Surgeons; ASOMP: Asian Society of Oral and Maxillofacial Pathology; JSOP: Japanese Society of Oral Pathol- ogy; JSOMS: Japanese Society of Oral and Maxillofacial Surgeons; JSOM: Japanese Society of Oral Medicine; JAMI: Japanese Academy of Maxillofacial Implants. ∗ Corresponding author at: PO Box 6700, Mulaidah, Buraidah 51452, Al Qassim, Saudi Arabia. Tel.: +966 6 380 0050x2049; fax: +966 6 380 1762. E-mail addresses: dr.hamdy.metwaly@qudent.org, hamdym66@gmail.com (H. Metwaly). the population [1,2]. The oral lesion may be associated with the skin and genital lesions, or it may be the only disease manifestation [3]. It typically affects middle-aged or elderly women, although it can be detected also in younger men, but rarely in children. Clinically, the most prevalent type of OLP is the reticular form characterized with interlacing white lines that are usually bilaterally distributed on the buccal mucosa and sometimes on the tongue. Other types of OLP are papular, plaque-like, atrophic, erosive and bullous forms [1,2]. Oral precancerous condition as accepted by the World Health Organization is defined as a generalized pathological state of oral mucosa associated with a significantly increased risk of cancer [4]. Malignant transformation has been estimated to occur in 0.5–2.9% of the OLP patients [5]. The histopathology of OLP is character- ized by a band-like lymphocytic infiltrate in subepithelial lamina 2212-5558/$ – see front matter © 2013 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd. All rights reserved.  http://dx.doi.org/10.1016/j.ajoms.2013.09.009