Original Contribution Immunohistochemical expression of p16 protein in oral squamous cell carcinoma and lichen planus Jahanshah Salehinejad, DMD, MS a , Nourieh Sharifi, MD, MS b , Maryam Amirchaghmaghi, DMD, MS c , Narges Ghazi, DMD, MS a, ⁎, Mohammad Taghi Shakeri, MSc, PhD d , Ala Ghazi, DMD e a Dental Research Center, Department of Oral and Maxillofacial Pathology, School of Dentistry, Mashhad University of Medical Sciences, Mashhad, Iran b Department of Pathology, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran c Oral and Maxillofacial Diseases Research Center, Department of Oral Medicine, School of Dentistry, Mashhad University of Medical Sciences, Mashhad, Iran d Department of Community Medicine and Public Health, Mashhad University of Medical Sciences, Mashhad, Iran e Department of Oral Medicine, School of Dentistry, Mashhad University of Medical Sciences, Mashhad, Iran abstract article info Available online xxxx Keywords: Lichen planus Squamous cell carcinoma p16 Epithelial carcinogenesis is a multistep process. Specific genetic events lead to malignant transformation of oral epithelium. Oral squamous cell carcinoma (OSCC) may be preceded by potentially malignant lesions such as oral lichen planus (OLP). The p16 protein functions as a negative regulator of the cell cycle progression. Altered pattern of p16 serves as a biomarker for oral mucosal dysplasia and malignant growth. The purpose of this study was to evaluate p16 expression in OSCC and OLP to determine whether it can be a useful marker for early detection of carcinogenesis. We examined p16 expression in 45 OSCCs (15 grade I, 15 grade II, and 15 grade III), 15 OLPs without dysplasia, and 8 normal mucosal specimens with immunohistochemistry. p16 was interpreted as positive if more than 70% of tumor cells showed brown nuclear and cytoplasmic staining. All of the OSCC and control group samples showed negative immunoreactivity, whereas 26.7% of OLP samples were positive for p16. Our findings suggest that p16 expression could not be used as a helpful marker for detection of development toward malignancy in OLP samples. © 2014 Elsevier Inc. All rights reserved. 1. Introduction Epithelial carcinogenesis is a multistep process [1]. Transmission from normal oral epithelium to oral dysplasia and cancer is believed to result from several genetic alterations [2,3]. Carcinoma of oral mucosa is the end result of this multistep process, which in most cases occurs earlier than morphological changes of the epithelium. Therefore, morphological alterations are not always predictive of a possible progression toward carcinoma [4,5]. Evaluation of the specific genetic events that lead to malignant transformation has been the subject of many different researches [5]. Moreover, in clinical application, molecular diagnostic markers can be useful for recognition of malignant transformation. The p16 protein, whose gene maps on 9p21, functions as a negative regulator of the cell cycle progression. It binds to and inhibits ck4- and ck6-mediated phosphorylation of retinoblastoma, thus blocking cell cycle progression from G1 to S phase. Apparently, p16 protein expression may occur in relation to the functional inactivation of Rb protein [2,6]. As variable results have been demonstrated in immunohistochemical studies of p16 in head and neck squamous cell carcinomas (HNSCCs) and oral premalignant lesions, evaluation of this marker has been the focus of some studies. Head and neck squamous cell carcinoma remains a major cause of morbidity and mortality worldwide [7]. Ninety percent of head and neck cancers are squamous cell carcinomas (SCCs), and more than 50% of tumors arise in the oral cavity [8]. Oral squamous cell carcinoma (OSCC) may be preceded by potentially malignant lesions such as oral lichen planus (OLP). Oral lichen planus is a relatively common chronic inflammatory autoimmune disease involving cytotoxic T lymphocytes activity against the epithelial cells [9,10]. The OLP lesions are more persistent than the dermal lesions and have been reported to carry a risk of malignant transformation to OSCC [11]. In the present study, we determined p16 expression in OSCC and OLP to evaluate whether it can be a useful marker for early detection of carcinogenesis. 2. Materials and methods Sixty-eight samples including 45 OSCCs (15 grade I or well differentiated, 15 grade II or moderately differentiated, and 15 grade III or poorly differentiated), 15 OLPs without dysplasia, and 8 normal mucosal specimens (control group) were retrieved from the files of Annals of Diagnostic Pathology xxx (2014) xxx–xxx ⁎ Corresponding author. Dental Research Center, Department of Oral and Maxillofacial Pathology, School of Dentistry, Mashhad University of Medical Sciences, Vakilalbad Blvd, PO Box 911735-984, Mashhad, Iran. Tel.: +98 511 8829501; fax: +98 511 8829500. E-mail address: ghazin@mums.ac.ir (N. Ghazi). http://dx.doi.org/10.1016/j.anndiagpath.2014.03.009 1092-9134/© 2014 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Annals of Diagnostic Pathology Please cite this article as: Salehinejad J, et al, Immunohistochemical expression of p16 protein in oral squamous cell carcinoma and lichen planus, Ann Diagn Pathol (2014), http://dx.doi.org/10.1016/j.anndiagpath.2014.03.009