Indian Journal of Dental Research

: 2020  |  Volume : 31  |  Issue : 2  |  Page : 277--281

PECAM-1 overexpression signifies aggressive biologic behavior of oral lichen planus – A pilot study

A Lavanya, Wafa Khan, Preeti Singh, Dominic Augustine, Roopa S Rao, SV Sowmya, Vanishri C Haragannavar, K Shwetha Nambiar 
 Department of Oral Pathology and Microbiology, Faculty of Dental Sciences, M S Ramaiah University of Applied Sciences, M S R Nagar, Bangalore, Karnataka, India

Correspondence Address:
Dr. A Lavanya
Department of Oral Pathology and Microbiology, Faculty of Dental Sciences, M S Ramaiah University of Applied Sciences, M S R Nagar, Bangalore . 560 054, Karnataka


Context: The etiopathogenesis of oral lichen planus (OLP) is still debatable. According to literature, many studies have illustrated OLP as a T-cell-mediated chronic autoimmune disease. Currently, there is increased evidence of chronic inflammation in OLP and its association with vascular adhesion molecules (VAMs). Aim: The aim of this study was to evaluate the expression of VAM (PECAM-1) in OLP. Setting and Design: Tissue samples involved 20 archival cases of histopathologically confirmed OLP (n = 15) and normal mucosa (n = 5) as controls. Materials and Methods: The sections were subjected to immunohistochemical analysis using antibody to PECAM-1. Brown staining of the endothelial cells of blood vessels was considered positive. The expression of PECAM-1 in OLP was statistically analyzed using Wilcoxon sign-rank test. Results: The expression of PECAM-1 in OLP was statistically significant when compared with normal mucosa (P < 0.05). A statistically significant difference was also observed in PECAM-1 expression between the reticular type and erosive type of OLP. Conclusion: PECAM-1 was found to be overexpressed in OLP; difference in PECAM-1 expression was noted between the reticular and erosive types. The VAMs could be exploited as a possible therapeutic target in OLP to modulate the disease process thereby reducing the dependency on corticosteroids.

How to cite this article:
Lavanya A, Khan W, Singh P, Augustine D, Rao RS, Sowmya S V, Haragannavar VC, Nambiar K S. PECAM-1 overexpression signifies aggressive biologic behavior of oral lichen planus – A pilot study.Indian J Dent Res 2020;31:277-281

How to cite this URL:
Lavanya A, Khan W, Singh P, Augustine D, Rao RS, Sowmya S V, Haragannavar VC, Nambiar K S. PECAM-1 overexpression signifies aggressive biologic behavior of oral lichen planus – A pilot study. Indian J Dent Res [serial online] 2020 [cited 2021 Dec 8 ];31:277-281
Available from:

Full Text


OLP is a chronic mucocutaneous inflammatory disease that affects the mucous membrane and skin. It affects 1%–2% of the population. It presents clinically as reticular, papular, plaque-like, erosive, atrophic, or bullous types.[1] The World Health Organization (WHO) has categorized OLP as an oral potentially malignant disorder. The most significant complication of OLP is transformation into oral squamous cell carcinoma (OSCC).[1] A meta-analysis by Aghbari SM et al. in 2017 stated that 1.1% of OLP cases transform into OSCC with a higher incidence in alcohol users, smokers, and in individuals with hepatitis infection. Erosive lichen planus has the highest potential for malignant transformation to progress into OSCC compared with the other clinical types of OLP.[2] Despite efforts invested clinicopathologically, conflicting results and varied opinions leave many unanswered questions regarding its exact etiopathogenesis. Although topical corticosteroids have been used to treat OLP, complete cure if not achieved is due to frequent recurrences. Two theories of etiopathogenesis are mainly considered in OLP, which are T-cell-mediated and cytokine-mediated upregulation of adhesion molecules.[3] Currently, studies proposed that the pathogenesis of oral lichen planus (OLP) is mediated by migration of T cells at the site of damage and interaction with leucocytes mediated by cell surface adhesion molecules. These molecules play a significant role in regulating immune functions that include adhesion to endothelial cells and lymphocyte migration into extravasal tissues. There are a number of VAMs present such as ICAM- 1, VCAM-1, PECAM-1, ELAM-1, P-selectin, CD 34, and E-cadherin.[4],[5]

VAMs are involved in a positive feedback loop, where an inflammatory state promotes angiogenesis which in turn facilitates chronic inflammation. This results in an increased inflammatory infiltrate, progression, and recurrence of the lesions. Targeting the vascular adhesion molecules (VAMs) may unlock new treatment strategies.[6] Based on literature review, PECAM-1 has been scarcely researched in OLP, hence the aim of this study was to assess the role of VAM – (PECAM-1) in etiopathogenesis of OLP.

 Materials And Methods

Case selection

Following approval of Ethics Committee, archival tissue was retrieved from the Department of Oral Pathology and Microbiology, Faculty of Dental Sciences, M S Ramaiah University of Applied Sciences. The cases comprised 15 paraffin-embedded tissue blocks of OLP (10 males and 5 females) clinically and histopathologically diagnosed according to WHO 2003 criteria.[3],[5] Cases of normal mucosa were used as a control.

Immunohistochemical analysis

Tissue sections of cases and controls were initially prepared for routine hematoxylin and eosin staining. Serial sections of 4–6 μm thickness were prepared on silane-coated slides for immunohistochemical (IHC) analysis. The sections were deparaffinized and were rehydrated through different grades of alcohol. Endogenous peroxidase activity in tissue sections was then blocked by immersing the slides in phosphate buffer saline (PBS) containing 0.6% hydrogen peroxide. Antigen retrieval was performed in three cycles using microwave technique. IHC staining was performed with primary antibody, monoclonal mouse anti-human PECAM-1 (DAKO Diagnostics, Denmark; IR503, clone F7.2.38, dilution 1:100). The slides were washed with PBS for 5 min at room temperature followed by incubation with secondary antibody labeled with avidin–biotin peroxidase. The slides were washed with PBS for 5 min at room temperature and were treated with 3,3-diaminobenzidine chromogen. Counter-staining of the tissue sections was done with Harris hematoxylin for 2 min and washed in running tap water for 5 min. Dehydration was performed with increased concentrations of alcohol. The slides were immersed in xylene for 6 min at room temperature and mounted with Distrene dibutyl phthalate xylol for interpretation.


The IHC-stained slides were scored by three investigators. Brown staining of endothelial cells was considered positive for PECAM-1 expression. The stained cells were counted in five selected microscopic fields. The immunopositivity for PECAM-1 was semi-quantitatively assessed by scoring criteria proposed by Regezi et al. in 1996.[5] The cases were categorized as follows: 0 = negative staining, + = slight staining, ++ = moderate staining, and +++ = intense staining.

Statistical analysis

Wilcoxon sign-rank test was used to analyze the results obtained. Statistical calculations were performed with the use of Statistical Package for Social Sciences (SPSS) version 22.0 (IBM Corp., Armonk, New York., USA). Probability values less than 0.05 were considered as significant.


PECAM -1 expression in OLP and control tissue

In this study, all the 15 cases of OLP showed positivity for PECAM-1. All the five cases of normal mucosa taken as controls showed slight staining for PECAM-1 [Figure 1], [Table 1]. In erosive OLP, all the eight cases showed intense staining for PECAM-1 [Figure 2]; however, in reticular OLP, six cases showed moderate staining [Figure 3] and one case displayed slight staining [Figure 4], [Table 2]. PECAM-1 expression levels in OLP and control tissue were found to be statistically significant (P = 0.034) as shown in [Table 3]. Statistically significant difference was also observed between the erosive and reticular types of OLP (P = 0.011) as shown in [Table 4]. PECAM-1 expression was observed more in the inflammatory infiltrate area than deeper stroma.{Figure 1}{Table 1}{Figure 2}{Figure 3}{Figure 4}{Table 2}{Table 3}{Table 4}


The description of lichen planus is generally attributed to Ferdinand Ritter von Hebra, and he termed the condition as “lichen ruber planus.” Later, Erasmus Wilson and Moritz Kaposi simplified the name to “lichen planus.” In 1866, Wilson described the term “oral lichen planus” by noticing the white papular eruption of tongue and buccal mucosa. Clinically, there are six types of OLP which are reticular, atrophic, erosive, bullous, papular, and plaque types. The erosive type of OLP has the highest potential for malignant transformation ranging from 0.3% to 3.5%. The exact etiopathological mechanism of OLP is still unclear.[7],[8]

Several studies have evaluated different VAMs in OLP; however, PECAM-1 has been analyzed in only one study earlier.[5] Regezi et al. in 1996 reported PECAM-1 expression in 10 cases of OLP and concluded that PECAM-1 is overexpressed in OLP.[5] PECAM-1 expression pertaining to the clinical subtypes was not addressed.

VAMs are proteins which play an important role in providing interaction between lymphocytes and endothelium. It is proposed that VAMs like PECAM-1, VCAM1, ICAM1, and ELAM1 play a significant role in lymphocytic activation and lymphocytic trafficking by an increase in LFA-1, L-selectin, and VLA4 receptors. In normal conditions, a small amount of VAMs is expressed by endothelial cells, but increased expression has been observed in various inflammatory conditions as well.[3],[4]

In 2002, Dorrego et al. proposed that a higher expression of VCAM1 and ICAM1 in OLP could be an activating factor for CD8+ lymphocytes leading to the chronic form of the disease.[9] In 2003, Little et al. showed that adhesion molecules ICAM1 and RANTES were expressed by oral mucosal keratinocytes in OLP and amalgam induced oral lichenoid reactions suggesting that keratinocytes could be a key inflammatory trigger mechanism.[10] Similarly, Sangeetha et al. in 2011 stated that the expression of ELAM1, VCAM1, and ICAM1 in OLP was increased by endothelial cells of the subepithelial vascular network, and activated T cells show increased migration mediated by VCAM1 and ICAM1.[11] Lage et al. in 2012 found an increase in ICAM1-expressing cells in OLP and lichenoid-drug-induced eruption with no significant difference between the groups.[12]

In this study, a statistically significant difference for PECAM-1 expression was observed between OLP and normal mucosa (P = 0.034). When the erosive and reticular types were compared, all cases of erosive lichen planus (eight cases) showed intense PECAM-1 expression compared with the reticular type (six cases) which showed moderate staining intensity, and one case of the reticular type showed slight expression. A statistical significance for PECAM-1 expression was observed between the reticular and erosive types of OLP (P = 0.011). This indicates that PECAM-1 expression correlates with aggressive behavior of OLP.

Based on the results obtained, VAM is increased in OLP particularly erosive when compared with the reticular type. This could possibly suggest that VAM is a contributing factor for higher malignant potential in the erosive form.[4] The use of VAM as an early diagnostic marker for malignant transformation in OLP needs to be investigated on a large sample size. Currently, researchers proved that the risk of developing squamous cell carcinoma in patients with OLP is approximately 10 times greater than that in the unaffected population. The malignant transformation of OLP ranges from 0.4% to 5%.

An increase in VAMs and cytokines is necessary for lymphocytic infiltration toward the basal cells. These vascular adhesion factors act as signal proteins and help in communication between endothelium and T cells. Recently, various studies stated that the macrophages, factor-XIIIa-positive dendrocytes, lymphocytes, and langerhans cells are the source of cytokines like tumor necrosis factor–alpha and interleukin-1 in OLP. The results of this study indicate the role of PECAM-1 in sustaining the inflammatory components in OLP and thereby perpetuating the disease.[3],[6],[7] Recent concepts in treatment of OLP include corticosteroid therapy and immunomodulatory drugs such as levamisole, calcineurin inhibitors, retinoids, dapsone, hydroxychloroquine, mycophenolate mofetil, and enoxaparin. Despite the usage of these drugs, exacerbation of lesions is common in OLP, and its uncertain mechanism of malignant transformation is poorly understood.[13],[14],[15]

The VAMs could contribute to increased angiogenesis that leads to recruitment and retention of lymphocytes and progression of disease or exacerbation of lesions. Presence of a persistent inflammatory component may trigger carcinogenesis.[6]


Although OLP can be diagnosed clinically, biopsy is the gold standard to confirm the diagnosis. However, recurrences are common even with appropriate treatment. Hence, understanding the pathogenesis of OLP is important for definite therapeutic management. This would help in preventing further progression of the disease and possible malignant transformation. This study revealed that PECAM-1, a VAM, showed higher expression in OLP especially in the erosive type, supporting the role of VAM and angiogenesis in the etiopathogenesis of OLP. Hence, VAMs seem to play a pivotal role in pathogenesis of OLP and its role in malignant transformation is yet to be established; studies on a larger sample size with selection of subtypes and appropriate follow-up are the need of the hour.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


1Neville BW, Damm DD, Chi AC, Allen CM. Oral and Maxillofacial Pathology. 4th ed. Philadelphia: Saunders; 2009.
2Aghbari SM, Abushouk AI, Attia A, Elmaraezy A, Menshawy A, Ahmed MS, et al. Malignant transformation of oral lichen planus and oral lichenoid lesions: A meta-analysis of 20095 patient data. Oral Oncol 2017;68:92-102.
3Lavanya N, Jayanthi P, Rao UK, Ranganathan K. Oral lichen planus: An update on pathogenesis and treatment. J Oral Maxillofac Pathol 2011;15:127-32.
4Seyedmajidi M, Shafaee S, Bijani A, Bagheri S. VCAM1 and ICAM1 expression in oral lichen planus. Int J Mol Cell Med 2013;2:34-40
5Regezi JA, Dekker NP, MacPhail LA, Lozada-Nur F, McCalmont TH. Vascular adhesion molecules in oral lichen planus. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996;81:682-90.
6Mittal N, Shankari GM, Palaskar S. Role of angiogenesis in the pathogenesis of oral lichen planus. J Oral Maxillofac Pathol 2012;16:45-8.
7Gupta S, Jawanda MK. Oral lichen planus: An update on etiology, pathogenesis, clinical presentation, diagnosis and management. Indian J Dermatol 2015;60:222-9.
8Chitturi RT, Devy AS, Nirmal RM, Sunil PM. Oral lichen planus: A review of etiopathogenesis, clinical, histological and treatment aspects. J Interdiscipl Med Dent Sci 2014;2:142.
9Dorrego MV, Correnti M, Delgado R, Tapia FJ. Oral lichen planus: Immunohistology of mucosal lesions. J Oral Pathol Med 2002;31:410-4.
10Little M, Griffiths C, Watson R, Pemberton MN, Thornhill MH. Oral mucosal keratinocytes express RANTES and ICAM-1, but not interleukin-8, in oral lichen planus and oral lichenoid reactions induced by amalgam fillings. Clin Exp Dermatol 2003;28:64-9
11Sangeetha S, Victor D. The molecular aspects of oral mucocutaneous diseases: A review. Int J Genet Mol Biol 2011;3:141-8.
12Lage D, Juliano PB, Metze K, Souza EM, Cintra ML. Lichen planus and lichenoid drug-induced eruption: A histological and immunohistochemical study. International Journal of Dermatology 2012;51:1199-205.
13Usatine RP, Tinitigan M. Diagnosis and treatment of lichen planus. Am Fam Physician 2011;1:53-60.
14Patil S, Rao RS, Sanketh DS, Sarode SC, Sarode GS. A universal diagnostic criteria for oral lichen planus: An exigency!Int J Contemp Dent Med Rev 2014;2014. Article ID 041214. doi: 10.15713/ins.ijcdmr.15.
15Ahmed SS, Gadalla LM, Elmeadawy SH, Badria F. The efficacy of Aloe vera gel in treatment of oral lichen planus. Int Dent Med J Adv Res 2018;4:1-6.