1. bookVolume 75 (2021): Issue 2 (April 2021)
Journal Details
First Published
14 Sep 2008
Publication timeframe
6 times per year
access type Open Access

Expression and Localisation of CD44 Antigen as a Prognostic Factor of Oral Leukoplakia

Published Online: 08 May 2021
Page range: 68 - 74
Received: 10 Jul 2020
Accepted: 02 Mar 2021
Journal Details
First Published
14 Sep 2008
Publication timeframe
6 times per year

It is essential to identify markers that could indicate the presence of early molecular changes in premalignant tissues like oral leukoplakia (OL). CD44 adhesion molecule is not only a stem cell marker, but also determines cell proliferation and migration in malignant processes. The aim of our study was to assess the amount and pattern of CD44 antigen expression by epithelial and mononuclear cells in the lamina propria under OL and their role in premalignant lesions. The current study included 102 cases of OL and ten biopsies from healthy oral mucosa. Immunohistochemical CD44 antigen expression was determined in 34 cases by a standard EnVision imaging system in three points of OL: both edges and centre. Statistical analysis was done using GraphPad Prism software version 8.4.0. In OL, statistically significant overexpression of membranous CD44 was demonstrated compared to healthy mucosa (p < 0.0001). The intra-cytoplasmatic CD44 expression of epithelium together with characteristic nuclear changes may be used as a predictive factor for potential malignant transformation of non-homogenous leukoplakia. CD44 expression in mononuclear cells under the basal membrane in OL (p < 0.05) possibly influences the process of premalignant lesion transformation into intraepithelial cancer. Further study of CD44 antigen expression in intra-cytoplasmatic structures is required for better explanation of the role of this glycoprotein.


Alsalem, B. (2019). The diagnostic utility of cancer stem cell marker CD44 in early detection of oral cancer. Dissertation, Thesis Master of Science, University of Maryland, Baltimore. https://archive.hshsl.umaryland.edu/handle/10713/11708 (accessed 20.03.2021).Search in Google Scholar

Ambele, M. A,, van Zyl, A., Pepper, M. S., van Heerden, M. B., Heerden, W. F. P. (2020). Amplification of 3q26.2, 5q14.3, 8q24.3, 8q22.3, and 14q32.33: Are possible common genetic alterations in oral cancer patients. Frontiers Oncol., 10, 1-8.Search in Google Scholar

Alves, C. S., Yakovlev, S., Medved, L., Konstantopoulos, K. (2009). Bio-molecular characterization of CD44-fibrin(ogen) binding: Distinct molecular requirements mediate binding of standard and variant isoforms of CD44 to immobilized fibrin(ogen). J. Biol Chem.,284 (2), 1177–1189.Search in Google Scholar

Anonymous (2020). GLOBOCAN, 2018. http://gco.iarc.fr (accessed 29.06.2020).Search in Google Scholar

Assimakopoulos, D., Kolettas, E., Patrikakos, G., Evangelou, A. (2002). The role of CD44 in the development and prognosis of head and neck squamous cell carcinomas. Histol. Histopathol., 17 (4), 1269–1281.Search in Google Scholar

Boxberg, M., Götz, C., Haidari S., Dorfner, C., Jesinghaus, M., Drecoll, E., Boskov, M., Wolff, K. D., Weichert, W., Haller, B., Kolk, A. (2018). Immunohistochemical expression of CD44 in oral squamous cell carcinoma in relation to histomorphological parameters and clinicopathological factors. Histopathology, 73 (4), 559–572.Search in Google Scholar

Chen, D., Cun-YuWang, C.-Y (2019). CD44 and ALDH1 immuno-expression as prognostic indicators of invasion and metastasis in oral squamous cell carcinoma. Precision Clin. Med., 2 (3), 152–165.Search in Google Scholar

Diz, P., Meleti, M., Diniz-Freitas, M., Vescovi, P., Warnakulasuriya, S., Johnson, N. W., Kerr, A. K. (2017). Oral and pharyngeal cancer in Europe: Incidence, mortality and trends as presented to the Global Oral Cancer Forum. Transl. Res. Oral Oncol., 2, 1–3Search in Google Scholar

Garcia, A. S., Assao, A., Carvalho, A. L., Soares F. A., Koalski L. P., Oliveira D. T. (2019). The stem cell markers expression CD44v6 and podoplanin in lip cancer: Clinical significance. Virchows Arch., 474 (6), 745–754.Search in Google Scholar

Godge, P. Y., Poonja L. S. (2011). Quantitative assessment of expression of cell adhesion molecule (CD44) splice variants: CD44 standard (CD44s) and v5, v6 isoforms in oral leukoplakias: an immunohistochemical study. Indian J. Dent Res.,22 (3), 493–494Search in Google Scholar

Gore, Y., Starlets, D., Maharshak, N., Becker-Herman, S., Kaneyuki, U., Leng, L., Bucala, R., Shachar, I. (2008). Macrophage migration inhibitory factor induces B cell survival by activation of a CD74-CD44 receptor complex. J. Biol. Chem., 283 (5), 2784–2792.Search in Google Scholar

Groma, V., Kazanceva, A., Krukle, Z. N., Murovska, M. (2012). Oropharyngeal malignant epithelial cell, lymphocyte, and macrophage CD44 surface receptors for hyaluronate are expressed in sustained EBV infection: Immunohistochemical data and EBV DNA tissue indices. Pathol. Res. Practice,208 (9), 518–526.Search in Google Scholar

Harada, H., Takahashi, M. (2007). CD44-dependeent intracellular and extracellular catabolism of hyaluronic acid by hyaluronidase-1 and -2. J. Biol. Chem., 282, 5597–5607.Search in Google Scholar

Herold-Mende, C., Seiter, S., Born, A. I., Patzelt, E., Schupp, M., Zölle, J., Bosch, F. X., Zöller, M. (1996). Expression of CD44 splice variants in squamous epithelia and squamous cell carcinomas of the head and neck. J. Pathol., 179 (1), 66–73.Search in Google Scholar

Jakovlevs, A., Vanags, A., Gardovskis, J., Strumfa, I. (2019). Molecular classification of diffuse gliomas. Pol. J. Pathol., 70 (4), 246–258.Search in Google Scholar

Johnson, P., Ruffell, B. (2009). CD44 and its role in inflammation and inflammatory diseases. Inflamm. Allergy-Drug Targets, 8 (3), 208–220.Search in Google Scholar

Kaza, S., Kantheti, L. P., Poosarla, C., Gontu, S. R., Kattappagari, K. K., Baddam, V. R. (2018). A study on the expression of CD44 adhesion molecule in oral squamous cell carcinoma and its correlation with tumor histological grading. J. Orofac. Sci., 10, 42–49.Search in Google Scholar

Khajuria, N., Metgud, R. (2015). Role of bacteria in oral carcinogenesis. Indian J. Dent., 6 (1), 37–43.Search in Google Scholar

Lindquist, D., Ahrlund-Richter, A., Tarjįn, M., Tot, T., Dalianis, T. (2012). Intense CD44 expression is a negative prognostic factor in tonsillar and base of tongue cancer. Anticancer Res. Act., 32 (1), 153–161.Search in Google Scholar

Miletti-González, K. E., Murphy, K., Kumaran, M. N., Ravindranath, A. K., Wernyj, R. P., Kaur, S., Miles, G. D., Lim, E., Chan, R., Chekmareva, M., Heller, D. S., Foran, D., Chen, W., Reiss, M., Bandera, E. V., Kathleen Scotto, K., Rodríguez-Rodríguez, L. (2012). Identification of function for CD44 intracytoplasmic domain (CD44-ICD): Modulation of matrix metalloproteinase (MMP-9) transcription via novel promoter response element. J. Biol. Chem., 287 (23), 18995–19007.Search in Google Scholar

Naga, S. K. S. V., Shekar, P. C., Kattappagari, K. K., Chandra, K. L. P., Reddy, G. S., Reddy, B. V. R. (2019). Expression of cluster differentiation-44 stem cell marker in grades of oral epithelial dysplasia: A preliminary study. J. Oral Maxillofac. Pathol., 23 (2), 203–207.Search in Google Scholar

Nanci A. (2017). Ten Cate’s Oral Histology: Development, Structure and Function.9th edn. St. Luis, Elsevier. 352 pp.Search in Google Scholar

Narayan, T. V., Shilpashree, S. (2016). Meta-analysis on clinicopathologic risk factors of leukoplakias undergoing malignant transformation. J. Oral Maxillofac. Pathol.,20 (3), 354–361.Search in Google Scholar

Negi, L. M., Talegaonkar, S., Jaggi, M., Iqbalz. Z., Khar, R. K. (2012). Role of CD44 in tumour progression and strategies for targeting. J. Drug Target., 20, 561–573.Search in Google Scholar

Ortiz, R. C., Lopes, N. M., Amor, N. G., José, B. P., Schmerling, C. K., Lara V. S., Moyses, R. A., Rodini, C. O. (2018). CD44 and ALDH1 immuno-expression as prognostic indicators of invasion and metastasis in oral squamous cell carcinoma. J. Oral Pathol. Med., 47, 740–747.Search in Google Scholar

Pettersen, J. S., Fuentes-Duculan, J., Suįrez-Farińas, M., Pierson, K. C., Pitts-Kiefer, A., Fan, L., Belkin, D. A., Wang, C. Q. F., Bhuvanendran, S., Johnson-Huang, L. M., Bluth, M. J., Krueger, J. G., Lowes, M. A., Carucci, J. A. (2011). Tumor-associated macrophages in the cutaneous SCC micro-environment are heterogeneously activated. J. Invest. Dermat., 131 (6),1322–1330.Search in Google Scholar

Pisterna, G. V., Siragusa, M. (2007). CD44 presence in inflamed pulp tissue. J. Endod., 33 (10), 1203–1207.Search in Google Scholar

Puré, E., Oaff, C. A. (2001). A crucial role for CD44 in inflammation. Trends Mol. Med., 7 (5), 213–221.Search in Google Scholar

Reid, P., Marcu, L. G., Olve, I., Moghaddasi, L., Staudacher, A. H., Bezak, E. (2019). Diversity of cancer stem cells in head and neck carcinomas: The role of HPV in cancer stem cell heterogeneity, plasticity and treatment response. Radiother. Oncol.,135, 1–12.Search in Google Scholar

Renaud-Vilmer, C., Cavelier-Balloy, B. (2017). Precancerous lesions of the buccal epithelium. Ann. Dermatol. Venereol., 144 (2), 100–108.Search in Google Scholar

Roye, D. G., Myers, R. B., Brown, D., Poczatek, D. R., Beenken S. W., Grizzle, W. E. (1996). CD44 expression in dysplastic epithelium and squamous-cell carcinoma of the esophagus. Int. J. Cancer, 69, 254–258.Search in Google Scholar

Speight, P. M., Khurram, S. A., Kujan, O. (2018). Oral potentially malignant disorders: Risk of progression to malignancy. Oral Surg. Oral Med. Oral Pathol. Oral Radiol., 125 (6), 612–627.Search in Google Scholar

Sundberg, J., Korytowska, M., Holmberg, E., Bratel, J., Wallström, M., Kjellström, E., Blomgren, J., Kovįcs, A., Öhman, J., Sand, L., Hirsch, J.-M., Giglio, D., Kjeller, G., Bengt Hasséus, B. (2019). Recurrence rates after surgical removal of oral leukoplakia: A prospective longitudinal multi-centre study. PLoS One, 14 (12), e0225682.Search in Google Scholar

Tamatani, T., Takamaru, N., Ohe, G., Akita, K., Nakagawa, T., Miyamoto, Y. (2018). Express of CD44, CD44v9, ABCG2, CD24, Bmi-1 and ALDH1 instage I and II oral squamous cell carcinoma and their association with clinicopathological factors. Oncol. Lett., 16 (1),1133–1140.Search in Google Scholar

Wang, S. J., Wong, G, de Heer G. A. M., Xia W, Bourguignon, L.Y. (2009). CD44 variant isoforms in head and neck squamous cell carcinoma progression. The Laryngoscope, 119 (8), 1518–1530.Search in Google Scholar

Warnakulasuriya S. (2009). Global epidemiology of oral and oropharyngeal cancer. Oral. Oncol., 45 (4–5), 309–316.Search in Google Scholar

Wielenga, V. J. M., Heider, K-H., Offerhaus, G. J. A., Adolf, G. R., Berg, F. M., Punta, H., Herrlich, P., Steven T. Pals, S. T. (1993). Advances in brief expression of CD44 variant proteins in human colorectal cancer is related to tumor progression. Cancer Research, 53, 4754–4756.Search in Google Scholar

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