CD146 expression in oral lichen planus and oral cancer

  • Sarinthon Pariyawathee
  • Ekarat Phattarataratip
  • Kobkan ThongprasomEmail author
Original Article



To examine the CD146/METCAM expression on keratinocytes in normal oral mucosa (NOM), oral lichen planus (OLP), oral epithelial dysplasia (OED), and oral squamous cell carcinoma (OSCC).

Subjects and methods

Immunohistochemical examination of CD146 was performed on 80 specimens, divided into 20 cases from each group. The number of CD146+ keratinocytes was quantitatively assessed together with the staining intensity.


The mean percentage of CD146+ keratinocytes was 19.04+15.32, 59.40+24.48, 60.04+28.87, and 22.13+21.03 in NOM, OLP, OED, and OSCC, respectively. The mean percentages of CD146+ keratinocytes in OLP and OED were significantly higher than those of NOM and OSCC (p≤0.001). Most OED (55%) and OLP (60%) showed strong and moderate staining intensity, respectively, while NOM (50%) and OSCC (45%) predominantly expressed CD146 at mild intensity.


This is the first study to examine CD146 expression in OLP and OED. CD146 is upregulated in OLP and OED but downregulated in OSCC. The alteration in CD146 may be involved in the immunoregulatory response of OLP and the early event of oral carcinogenesis. The loss of this protein may underlie the progression of OED into invasive OSCC.

Clinical relevance

Overexpression of CD146 protein may play a role in the pathophysiology of OLP and OED.


CD146 METCAM Oral epithelial dysplasia Oral lichen planus Oral squamous cell carcinoma 



We thank Mr. Koson Intarasut, Institute of Pathology, Bangkok, Thailand, for immunohistochemistry technical assistant, Dr. Kevin Tompkins for critical review of this manuscript, and Assistant Professor Dr. Soranun Chantarangsu for statistical analysis. Our thanks also go to the Oral Medicine and Oral Pathology staff at the Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand, for their assistance. We thank the Research Unit in Oral Diseases, Chulalongkorn University for long-term support.


This research was supported by the Faculty Research Grant (DRF 60020), Faculty of Dentistry, Chulalongkorn University 2017 and the 90 year of Chulalongkorn University, Rachadapiseksoompoch grant 2017.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The Ethics Committee of Chulalongkorn University, Faculty of Dentistry, approved this study protocol.

Informed consent

Informed consent was obtained from all individual participants included in this study.


  1. 1.
    Makrilia N, Kollias A, Manolopoulos L, Syrigos K (2009) Cell adhesion molecules: role and clinical significance in cancer. Cancer Investig 27:1023–1037. CrossRefGoogle Scholar
  2. 2.
    Huang YW, Baluna R, Vitetta ES (1997) Adhesion molecules as targets for cancer therapy. Histol Histopathol 12:467–477Google Scholar
  3. 3.
    Koukoulis GK, Patriarca C, Gould VE (1998) Adhesion molecules and tumor metastasis. Hum Pathol 29:889–892CrossRefGoogle Scholar
  4. 4.
    Wu GJ (2018) Dual role of METCAM/MUC18 expression in the progression of cancer cells. Book title. InTech 13:254–289Google Scholar
  5. 5.
    Ouhtit A, Gaur RL, Abd Elmageed ZY, Fernando A, Thouta R, Trappey AK, Abdraboh ME, El-Sayyad HI, Rao P, Raj MG (2009) Towards understanding the mode of action of the multifaceted cell adhesion receptor CD146. Biochim Biophys Acta 1795:130–136. Google Scholar
  6. 6.
    Lehmann JM, Holzmann B, Breitbart EW, Schmiegelow P, Riethmuller G, Johnson JP (1987) Discrimination between benign and malignant cells of melanocytic lineage by two novel antigens, a glycoprotein with a molecular weight of 113,000 and a protein with a molecular weight of 76,000. Cancer Res 47:841–845Google Scholar
  7. 7.
    Wang Z, Yan X (2013) CD146, a multi-functional molecule beyond adhesion. Cancer Lett 330:150–162. CrossRefGoogle Scholar
  8. 8.
    Pires FR, Shih Ie M, da Cruz Perez DE, de Almeida OP, Kowalski LP (2003) Mel-CAM (CD146) expression in parotid mucoepidermoid carcinoma. Oral Oncol 39:277–281CrossRefGoogle Scholar
  9. 9.
    Bardin N, Anfosso F, Masse JM, Cramer E, Sabatier F, Le Bivic A, Sampol J, Dignat-George F (2001) Identification of CD146 as a component of the endothelial junction involved in the control of cell-cell cohesion. Blood 98:3677–3684CrossRefGoogle Scholar
  10. 10.
    Bardin N, Moal V, Anfosso F, Daniel L, Brunet P, Sampol J, Dignat George F (2003) Soluble CD146, a novel endothelial marker, is increased in physiopathological settings linked to endothelial junctional alteration. Thromb Haemost 90:915–920. CrossRefGoogle Scholar
  11. 11.
    Shih IM (1999) The role of CD146 (Mel-CAM) in biology and pathology. J Pathol 189:4–11. CrossRefGoogle Scholar
  12. 12.
    Watson-Hurst K, Becker D (2006) The role of N-cadherin, MCAM and beta3 integrin in melanoma progression, proliferation, migration and invasion. Cancer Biol Ther 5:1375–1382CrossRefGoogle Scholar
  13. 13.
    Li Y, Yu JM, Zhan XM, Liu LL, Jin N, Zhang YX (2014) Correlation of CD146 expression and clinicopathological characteristics in esophageal squamous cell carcinoma. Oncol Lett 8:859–863. CrossRefGoogle Scholar
  14. 14.
    Liu WF, Ji SR, Sun JJ, Zhang Y, Liu ZY, Liang AB, Zeng HZ (2012) CD146 expression correlates with epithelial- mesenchymal transition markers and a poor prognosis in gastric cancer. Int J Mol Sci 13:6399–6406. CrossRefGoogle Scholar
  15. 15.
    Liu D, Du L, Chen D, Ye Z, Duan H, Tu T, Feng J, Yang Y, Chen Q, Yan X (2016) Reduced CD146 expression promotes tumorigenesis and cancer stemness in colorectal cancer through activating Wnt/beta-catenin signaling. Oncotarget 7:40704–40718. Google Scholar
  16. 16.
    Weninger W, Rendl M, Mildner M, Mayer C, Ban J, Geusau A, Bayer G, Tanew A, Majdic O, Tschachler E (2000) Keratinocytes express the CD146 (Muc18/S-endo) antigen in tissue culture and during inflammatory skin diseases. J Invest Dermatol 115:219–224. CrossRefGoogle Scholar
  17. 17.
    Fitzpatrick SG, Hirsch SA, Gordon SC (2014) The malignant transformation of oral lichen planus and oral lichenoid lesions: a systematic review. J Am Dent Assoc 145:45–56. CrossRefGoogle Scholar
  18. 18.
    Thongprasom K, Carrozzo M, Furness S, Lodi G (2011) Interventions for treating oral lichen planus. Cochrane Database Syst Rev Cd001168.
  19. 19.
    Lu R, Zhang J, Sun W, Du G, Zhou G (2015) Inflammation-related cytokines in oral lichen planus: an overview. J Oral Pathol Med 44:1–14. CrossRefGoogle Scholar
  20. 20.
    Prucktrakul C, Youngnak-Piboonratanakit P, Kanjanabuch P, Prueksrisakul T, Thongprasom K (2015) Oral lichenoid lesions and serum antinuclear antibodies in Thai patients. J Oral Pathol Med 44:468–474. CrossRefGoogle Scholar
  21. 21.
    van der Meij EH, van der Waal I (2003) Lack of clinicopathologic correlation in the diagnosis of oral lichen planus based on the presently available diagnostic criteria and suggestions for modifications. J Oral Pathol Med 32:507–512CrossRefGoogle Scholar
  22. 22.
    Thongprasom K, Luengvisut P, Wongwatanakij A, Boonjatturus C (2003) Clinical evaluation in treatment of oral lichen planus with topical fluocinolone acetonide: a 2-year follow-up. J Oral Pathol Med 32:315–322CrossRefGoogle Scholar
  23. 23.
    Lei X, Guan CW, Song Y, Wang H (2015) The multifaceted role of CD146/MCAM in the promotion of melanoma progression. Cancer Cell Int 15:3. CrossRefGoogle Scholar
  24. 24.
    Safadi RA, Al Jaber SZ, Hammad HM, Hamasha AA (2010) Oral lichen planus shows higher expressions of tumor suppressor gene products of p53 and p21 compared to oral mucositis. An immunohistochemical study. Arch Oral Biol 55:454–461. CrossRefGoogle Scholar
  25. 25.
    Wai Wong C, Dye DE, Coombe DR (2012) The role of immunoglobulin superfamily cell adhesion molecules in cancer metastasis. Int J Cell Biol 2012:340296. CrossRefGoogle Scholar
  26. 26.
    Lodi G, Scully C, Carrozzo M, Griffiths M, Sugerman PB, Thongprasom K (2005) Current controversies in oral lichen planus: report of an international consensus meeting. Part 1. Viral infections and etiopathogenesis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 100:40–51. CrossRefGoogle Scholar
  27. 27.
    Schulz C, Petrig V, Wolf K, Kratzel K, Kohler M, Becker B, Pfeifer M (2003) Upregulation of MCAM in primary bronchial epithelial cells from patients with COPD. Eur Respir J 22:450–456CrossRefGoogle Scholar
  28. 28.
    Berman R, Jiang D, Wu Q, Stevenson CR, Schaefer NR, Chu HW (2016) MUC18 regulates lung rhinovirus infection and inflammation. PLoS One 11:e0163927. CrossRefGoogle Scholar
  29. 29.
    Berman R, Huang C, Jiang D, Finigan JH, Wu Q, Chu HW (2014) MUC18 differentially regulates pro-inflammatory and anti-viral responses in human airway epithelial cells. J Clin Cell Immunol 5:e0163927. Google Scholar
  30. 30.
    Mehanna HM, Rattay T, Smith J, McConkey CC (2009) Treatment and follow-up of oral dysplasia - a systematic review and meta-analysis. Head Neck 31:1600–1609. CrossRefGoogle Scholar
  31. 31.
    Santosh AB, Jones T, Harvey J (2016) A review on oral cancer biomarkers: understanding the past and learning from the present. J Cancer Res Ther 12:486–492. CrossRefGoogle Scholar
  32. 32.
    Nakagaki T, Tamura M, Kobashi K, Koyama R, Fukushima H, Ohashi T, Idogawa M, Ogi K, Hiratsuka H, Tokino T, Sasaki Y (2017) Profiling cancer-related gene mutations in oral squamous cell carcinoma from Japanese patients by targeted amplicon sequencing. Oncotarget 8:59113–59122. CrossRefGoogle Scholar
  33. 33.
    Williams HK, Sanders DS, Jankowski JA, Landini G, Brown AM (1998) Expression of cadherins and catenins in oral epithelial dysplasia and squamous cell carcinoma. J Oral Pathol Med 27:308–317CrossRefGoogle Scholar
  34. 34.
    Lin JC, Chiang CF, Wang SW, Wang WY, Kwan PC, Wu GJ (2014) Significance of expression of human METCAM/MUC18 in nasopharyngeal carcinomas and metastatic lesions. Asian Pac J Cancer Prev 15:245–252CrossRefGoogle Scholar
  35. 35.
    Wu GJ (2016) Dual roles of Metcam in the progression of nasopharyngeal carcinomas. Book title SMGroup 5:1–23Google Scholar
  36. 36.
    Feller L, Altini M, Lemmer J (2013) Inflammation in the context of oral cancer. Oral Oncol 49:887–892. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Oral Medicine Department, Faculty of DentistryChulalongkorn UniversityBangkokThailand
  2. 2.Oral Pathology Department, Faculty of DentistryChulalongkorn UniversityBangkokThailand

Personalised recommendations