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VOLUME 12 , ISSUE 6 ( November-December, 2021 ) > List of Articles


Do Stemness Markers in Oral Erythroplakia Have a Role in Malignant Transformation: A Comprehensive Review

Prasanna Nichat, Johara M Cruz, Muralimani Mani, Gargi S Sarode, Vikrant R Patil, Muhammad S Zafar

Keywords : Cancer stem cells, Carcinogenesis, Epithelial Dysplasia, Erythroplakia, Malignant transformation, Oral squamous cell carcinoma

Citation Information : Nichat P, Cruz JM, Mani M, Sarode GS, Patil VR, Zafar MS. Do Stemness Markers in Oral Erythroplakia Have a Role in Malignant Transformation: A Comprehensive Review. World J Dent 2021; 12 (6):510-514.

DOI: 10.5005/jp-journals-10015-1873

License: CC BY-NC 4.0

Published Online: 24-11-2021

Copyright Statement:  Copyright © 2021; The Author(s).


Oral squamous cell carcinoma (OSCC)—one of the most common neoplasms of the head and neck region—accounts for 90% of cancer-related deaths. It is a well-known fact that cancer stem cells (CSCs) play a vital role in tumor progression, metastasis, drug and radiation resistance, and recurrence. Potentially malignant disorders are a group of lesions that demonstrate epithelial dysplasia and are more likely to precede squamous cell carcinoma of the oral cavity. Among the various potentially malignant disorders, erythroplakia, a non-scrapable red lesion of the oral mucosa, is the most aggressive exhibiting severe dysplasia. Carcinogenesis is a multistep and complex process commencing from exposure of carcinogen to development of malignancy. Among the various pathogenic mechanisms of carcinogenesis, the role of CSCs in the malignant transformation of erythroplakia has been less explored. With the available information, the present review aims to discuss the stemness markers associated with the erythroplakia and to establish its association with erythroplakia and the early onset of OSCCs.

  1. Scully C, Sudbø J, Speight PM. Progress in determining the malignant potential of oral lesions. J Oral Pathol Med 2003;32(5):251–256. DOI: 10.1034/j.1600-0714.2003.00108.x.
  2. Olinici D, Cotrutz CE, Mihali CV, et al. The ultrastructural features of the premalignant oral lesions. Rom J Morphol Embryol 2018;59(1): 243–248.
  3. Reichart PA, Philipsen HP. Oral erythroplakia—a review. Oral Oncol 2005;41(6):551–561. DOI: 10.1016/j.oraloncology.2004.12.003.
  4. Sudbo J, Reith A. Which putatively pre-malignant oral lesions become oral cancers?. Clinical relevance of early targeting of high-risk individuals. J Oral Pathol Med 2003;32(2):63–70. DOI: 10.1034/j.1600-0714.2003.00054.x.
  5. Bryne M, Reibel J, Mandel U, et al. Expression of mucin type carbohydrates may supplement histologic diagnosis in oral premalignant lesions. J Oral Pathol Med 1991;20(3):120–125. DOI: 10.1111/j.1600-0714.1991.tb00904.x.
  6. Holmstrup P, Thorn JJ, Rindum J, et al. Malignant development of lichen planus-affected oral mucosa. J Oral Pathol Med 1988;17(5): 219–225. DOI: 10.1111/j.1600-0714.1988.tb01528.x.
  7. Sacks PG. Cell, tissue and organ culture as in vitro models to study the biology of squamous cell carcinomas of the head and neck. Cancer Metastasis Rev 1996;15(1):27–51. DOI: 10.1007/BF00049486.
  8. Dalley AJ, Pitty LP, Major AG, et al. Expression of ABCG2 and Bmi-1 in oral potentially malignant lesions and oral squamous cell carcinoma. Cancer Med 2014;3(2):273–283. DOI: 10.1002/cam4.182.
  9. Woo S-B. Oral epithelial dysplasia and premalignancy. Head Neck Pathol 2019;13(3):423–439. DOI: 10.1007/s12105-019-01020-6.
  10. Bhatia A, Burtness B. Novel molecular targets for chemoprevention in malignancies of the head and neck. Cancers (Basel) 2017;9(12):113. DOI: 10.3390/cancers9090113.
  11. Feng J-Q, Xu Z-Y, Shi L-J, et al. Expression of cancer stem cell markers ALDH1 and Bmi1 in oral erythroplakia and the risk of oral cancer. J Oral Pathol Med 2013;42(2):148–153. DOI: 10.1111/j.1600-0714.2012.01191.x.
  12. Feng J-Q, Mi J-G, Wu L, et al. Expression of podoplanin and ABCG2 in oral erythroplakia correlate with oral cancer development. Oral Oncol 2012;48(9):848–852. DOI: 10.1016/j.oraloncology.2012. 03.015.
  13. McNamara KK, Kalmar JR. Erythematous and vascular oral mucosal lesions: a clinicopathologic review of red entities. Head Neck Pathol 2019;13(1):4–15. DOI: 10.1007/s12105-019-01002-8.
  14. Desai A, Yan Y, Gerson SL. Concise reviews: cancer stem cell targeted therapies: toward clinical success. Stem Cells Transl Med 2019;8(1): 75–81. DOI: 10.1002/sctm.18-0123.
  15. Nassar D, Blanpain C. Cancer stem cells: basic concepts and therapeutic implications. Annu Rev Pathol Mech Dis 2016;11(1):47–76. DOI: 10.1146/annurev-pathol-012615-044438.
  16. Yang X, Shi L, Zhou Z, et al. Podoplanin and ABCG2 expression in oral erythroplakia revisited: potential evidence for cancer stem cells driving the process of field cancerization. Oral Oncol 2020;101:104368. DOI: 10.1016/j.oraloncology.2019.07.011.
  17. Lumerman H, Freedman P, Kerpel S. Oral epithelial dysplasia and the development of invasive squamous cell carcinoma. Oral Surgery, Oral Med Oral Pathol Oral Radiol Endodontology 1995;79(3):321–329. DOI: 10.1016/S1079-2104(05)80226-4.
  18. Holmstrup P. Oral erythroplakia-what is it? Oral Dis 2018;24(1–2): 138–143. DOI: 10.1111/odi.12709.
  19. Sudbø J, Kildal W, Johannessen AC, et al. Gross genomic aberrations in precancers: clinical implications of a long-term follow-up study in oral erythroplakias. J Clin Oncol 2002;20(2):456–462. DOI: 10.1200/JCO.2002.20.2.456.
  20. Capocasale G, Panzarella V, Tozzo P, et al. Oral verruciform xanthoma and erythroplakia associated with chronic graft-versus-host disease: a rare case report and review of the literature. BMC Res Notes 2017;10(1):631. DOI: 10.1186/s13104-017-2952-7.
  21. van der WI, Scully C. 4. Potentially malignant disorders of the oral and oropharyngeal mucosa. Dent Update 2011;38(2):138–140. DOI: 10.12968/denu.2011.38.2.138.
  22. Bánóczy J. Oral cancer and precancerous lesions. Fogorv Sz 1997;90(Spec No:27):PMID: 9170723.
  23. Mithani S, Mydlarz W, Grumbine F, et al. Molecular genetics of premalignant oral lesions. Oral Dis 2007;13(2):126–133. DOI: 10.1111/j.1601-0825.2006.01349.x.
  24. Shi L, Jiang W, Liu W. Retrospective analysis of oral erythroplakia focused on multiple and multifocal malignant behavior. Oral Dis 2019;25(7):1829–1830. DOI: 10.1111/odi.13144.
  25. Yang X, Liu W. Bibliometric analysis of the top-cited articles on oral erythroplakia and leukoplakia. J Oral Pathol Med 2019;48(6):505–506. DOI: 10.1111/jop.12863.
  26. Nikitakis NG, Rassidakis GZ, Tasoulas J, et al. Alterations in the expression of DNA damage response-related molecules in potentially preneoplastic oral epithelial lesions. Oral Surg Oral Med Oral Pathol Oral Radiol 2018;125(6):637–649. DOI: 10.1016/j.oooo.2018.03. 006.
  27. Venkat Naga SS, Shekar P, Kattappagari K, et al. Expression of cluster differentiation-44 stem cell marker in grades of oral epithelial dysplasia: a preliminary study. J Oral Maxillofac Pathol 2019;23(2):203. DOI: 10.4103/jomfp.JOMFP_308_18.
  28. Liu S-Y, Feng I-J, Wu Y-W, et al. Implication for second primary cancer from visible oral and oropharyngeal premalignant lesions in betel-nut chewing related oral cancer. Head Neck 2017;39(7):1428–1435. DOI: 10.1002/hed.24777.
  29. Greer RO. Pathology of malignant and premalignant oral epithelial lesions. Otolaryngol Clin North Am 2006;39(2):249–275. DOI: 10.1016/j.otc.2005.11.002.
  30. Villa A, Villa C, Abati S. Oral cancer and oral erythroplakia: an update and implication for clinicians. Aust Dent J 2011;56(3):253–256. DOI: 10.1111/j.1834-7819.2011.01337.x.
  31. Feng J, Zhou Z, Shi L, et al. Cancer stem cell markers ALDH1 and Bmi1 expression in oral erythroplakia revisited: Implication for driving the process of field cancerization. J Oral Pathol Med 2020;49(1):96–99. DOI: 10.1111/jop.12955.
  32. Rhodus NL, Kerr AR, Patel K. Oral cancer. Dent Clin North Am 2014;58(2):315–340. DOI: 10.1016/j.cden.2013.12.004.
  33. Boy SC. Leukoplakia and erythroplakia of the oral mucosa--a brief overview. SADJ 2012;67(10):558–560.
  34. Nakahata K, Uehara S, Nishikawa S, et al. Aldehyde dehydrogenase 1 (ALDH1) Is a potential marker for cancer stem cells in embryonal rhabdomyosarcoma. PLoS One 2015;10(4):e0125454. DOI: 10.1371/journal.pone.0125454.
  35. Mortazavi H, Baharvand M, Mehdipour M. Oral potentially malignant disorders: an overview of more than 20 entities. J Dent Res Dent Clin Dent Prospects 2014;8(1):6–14. DOI: 10.5681/joddd.2014. 002.
  36. Smith J, Rattay T, McConkey C, et al. Biomarkers in dysplasia of the oral cavity: a systematic review. Oral Oncol 2009;45(8):647–653. DOI: 10.1016/j.oraloncology.2009.02.006.
  37. Shafer WG, Waldron CA. Erythroplakia of the oral cavity. Cancer 1975;36(3):1021–1028. DOI: 10.1002/1097-0142(197509)36:3<1021::AID-CNCR2820360327>3.0.CO;2-W.
  38. Jin G. Using biomarkers to detect oral cancer holds potential for saving lives when the cancer is most curable. Biomark Med 2010;4(6):835–838. DOI: 10.2217/bmm.10.105.
  39. Batlle E, Clevers H. Cancer stem cells revisited. Nat Med 2017;23(10):1124–1134. DOI: 10.1038/nm.4409.
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