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VOLUME 13 , ISSUE S2 ( Supplementary Issue 2, 2022 ) > List of Articles


Significance of SOX2 in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma: An Immunohistochemical Study

Sapna Chandran, Rekha K Pillai, Bindhu P Ramakrishnan, Priya Thomas

Keywords : Biomarker, Cancer stem cells, Immunohistochemistry, Oral epithelial dysplasia, Oral squamous cell carcinoma, SOX2

Citation Information :

DOI: 10.5005/jp-journals-10015-2148

License: CC BY-NC 4.0

Published Online: 31-12-2022

Copyright Statement:  Copyright © 2022; The Author(s).


Aim: The present study aimed to determine the role of SRY (sex-determining region Y)—box 2 (SOX2) as a potential marker of stemness and pluripotency and to compare its association with the normal oral mucosa (NOM), different grades of oral epithelial dysplasia (OED), and oral squamous cell carcinoma (OSCC). Materials and methods: A total of 70 study samples, including 30 cases of OED (10 each of mild, moderate, and severe dysplasia), 30 cases of OSCC [10 each of well-, moderate-, and poorly differentiated (WD, MD, and PD)], and 10 NOM samples were immunohistochemically stained to evaluate SOX2 association. Quantitative analysis was based on the percentage of positive cells with a scoring of 0–5 (0%, 1–10%, 11–30%, 31–50%, 51–80%, and >80%), and qualitative evaluation was based on the intensity of staining grading from 0–3 (negative, weak, moderate, and strong). Differences in staining intensity were evaluated using the Kruskal–Wallis test. Statistical comparison of positive cells among three groups was performed using one-way analysis of variance and a pairwise comparison within groups using Tukey analysis. Results: SOX2 expression was more prominent in OSCC than OED and weakest in normal mucosa. A significant increase in SOX2 expression was observed from mild to severe dysplasia, whereas the expression decreased from WDOSCC to PDOSCC. Conclusion: In conformity with the present study, SOX2 expression is seen to be upregulated in higher grades of OED and early OSCC. Thus, highlighting its role in identifying the potential lesions at an early stage. Clinical significance: Identification of cancer stem cells (CSCs) using biomarkers may help in the early detection of tumor development. SOX2 showing evidence of expressing these cells can be utilized as a definitive biomarker.

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  1. Geum DH, Roh YC, Yoon SY, et al. The impact factors on 5-year survival rate in patients operated with oral cancer. J Korean Assoc Oral Maxillofac Surg 2013;39(5):207–216. DOI: 10.5125/jkaoms.2013.39.5.207
  2. Sharma P, Saxena S, Aggarwal P. Trends in the epidemiology of oral squamous cell carcinoma in western UP: an institutional study. Indian J Dent Res 2010;21(3):316–319. DOI: 10.4103/0970-9290.70782
  3. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021;71(3):209–249. DOI: 10.3322/caac.21660
  4. Leemans CR, Braakhuis BJ, Brakenhoff RH. The molecular biology of head and neck cancer. Nat Rev Cancer 2010;11(1):9–22. DOI: 10.1038/nrc2982
  5. Haddad RI, Shin DM. Recent advances in head and neck cancer. N Engl J Med 2008;359(11):1143–1154. DOI: 10.1056/NEJMra0707975
  6. Baillie R, Tan ST, Itinteang T. Cancer stem cells in oral cavity squamous cell carcinoma: a review. Front Oncol 2017;7:112. DOI: 10.3389/fonc.2017.00112
  7. Al-Hajj M, Becker MW, Wicha M, et al. Therapeutic implications of cancer stem cells. Curr Opin Genet Dev 2004;14(1):43–47. DOI: 10.1016/j.gde.2003.11.007
  8. Choi S, Myers JN. Molecular pathogenesis of oral squamous cell carcinoma: implications for therapy. J Dent Res 2008;87(1):14–32. DOI: 10.1177/154405910808700104
  9. Fu TY, Hsieh IC, Cheng JT, et al. Association of OCT4, SOX2, and NANOG expression with oral squamous cell carcinoma progression. J Oral Pathol Med 2016;45(2):89–95. DOI: 10.1111/jop.12335
  10. Freier K, Knoepfle K, Flechtenmacher C, et al. Recurrent copy number gain of transcription factor SOX2 and corresponding high protein expression in oral squamous cell carcinoma. Genes Chromosomes Cancer 2010;49(1):9–16. DOI: 10.1002/gcc.20714
  11. Motahhary P, Sahebjamee M, Nasimi M, et al. Immunohistochemical expression of SOX2 in oral normal epithelial, dysplasia and squamous cell carcinoma. J Craniomaxillofacial Res 2018;5(2):79–84.
  12. Wuebben EL, Rizzino A. The dark side of SOX2: cancer - a comprehensive overview. Oncotarget 2017;8(27):44917–44943. DOI: 10.18632/oncotarget.16570
  13. Ren ZH, Zhang CP, Ji T. Expression of SOX2 in oral squamous cell carcinoma and the association with lymph node metastasis. Oncol Lett 2016;11(3):1973–1979. DOI: 10.3892/ol.2016.4207
  14. Baillie R, Itinteang T, Yu HH, et al. Cancer stem cells in moderately differentiated oral tongue squamous cell carcinoma. J Clin Pathol 2016;69(8):742–744. DOI: 10.1136/jclinpath-2015-203599
  15. Wegner M. From head to toes: the multiple facets of Sox proteins. Nucleic Acids Res 1999;27(6):1409–1420. DOI: 10.1093/nar/27.6.1409
  16. Weina K, Utikal J. SOX2 and cancer: current research and its implications in the clinic. Clin Transl Med 2014;3:19. DOI: 10.1186/2001-1326-3-19
  17. Fong H, Hohenstein KA, Donovan PJ. Regulation of self-renewal and pluripotency by SOX2 in human embryonic stem cells. Stem Cells 2008;26(8):1931–1938. DOI: 10.1634/stemcells.2007-1002
  18. Liu K, Lin B, Zhao M, et al. The multiple roles for SOX2 in stem cell maintenance and tumorigenesis. Cell Signal 2013;25(5):1264–1271. DOI: 10.1016/j.cellsig.2013.02.013
  19. Hussenet T, du Manoir S. SOX2 in squamous cell carcinoma: amplifying a pleiotropic oncogene along carcinogenesis. Cell Cycle 2010;9(8):1480–1486. DOI: 10.4161/cc.9.8.11203
  20. Arnold K, Sarkar A, Yram MA, et al. SOX2(+) adult stem and progenitor cells are important for tissue regeneration and survival of mice. Cell Stem Cell 2011;9(4):317–329. DOI: 10.1016/j.stem.2011.09.001
  21. Wilbertz T, Wagner P, Petersen K, et al. SOX2 gene amplification and protein overexpression are associated with better outcome in squamous cell lung cancer. Mod Pathol 2011;24(7):944–953. DOI: 10.1038/modpathol.2011.49
  22. de Vicente JC, Donate-Pérez Del Molino P, Rodrigo JP, et al. SOX2 expression is an independent predictor of oral cancer progression. J Clin Med 2019;8(10):1744. DOI: 10.3390/jcm8101744
  23. Züllig L, Roessle M, Weber C, et al. High sex determining region Y-box 2 expression is a negative predictor of occult lymph node metastasis in early squamous cell carcinomas of the oral cavity. Eur J Cancer 2013;49(8):1915–1922. DOI: 10.1016/j.ejca.2013.01.005
  24. Bates TJ, Mahsoub R, Thomson PJ, et al. PAX9 expression in potentially malignant disorders and early stage squamous cell carcinoma of the oral cavity. Oral Surg Oral Med Oral Pathol Oral Radiol 2015;119(3):e183. DOI: 10.1016/j.oooo.2014.07.359
  25. He K, Zhang L, Huang C, et al. CD163+ tumor-associated macrophages correlated with poor prognosis and cancer stem cells in oral squamous cell carcinoma. BioMed Res Int 2014;2014(2):838632. DOI: 10.1155/2014/838632
  26. Michifuri Y, Hirohashi Y, Torigoe T, et al. High expression of ALDH1 and SOX2 diffuse staining pattern of oral squamous cell carcinomas correlates to lymph node metastasis. Pathol Int 2012;62(10):684–689. DOI: 10.1111/j.1440-1827.2012.02851.x
  27. Qiao B, He B, Cai J, et al. The expression profile of Oct4 and Sox2 in the carcinogenesis of oral mucosa. Int J Clin Exp Pathol 2013;7(1):28–37.
  28. Wang QI, He W, Lu C, et al. Oct3/4 and Sox2 are significantly associated with an unfavorable clinical outcome in human esophageal squamous cell carcinoma. Anticancer Res 2009;29(4):1233–1241.
  29. Ge N, Lin HX, Xiao XS, et al. Prognostic significance of Oct4 and Sox2 expression in hypopharyngeal squamous cell carcinoma. J Transl Med 2010;8(1):94. DOI: 10.1186/1479-5876-8-94
  30. Krishnamurthy S, Nör JE. Head and neck cancer stem cells. J Dent Res 2012;91(4):334–340. DOI: 10.1177/0022034511423393
  31. Khan W, Augustine D, Rao RS, et al. Stem cell markers SOX-2 and OCT-4 enable to resolve the diagnostic dilemma between ameloblastic carcinoma and aggressive solid multicystic ameloblastoma. Adv Biomed Res 2018;7:149. DOI: 10.4103/abr.abr_135_18
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