Sobhy, A., Fouad, H., Riad, S., Zaitoun, I. (2019). EVALUATION OF SOX2 AS A POTENTIAL STEM CELL MARKER IN BENIGN AND MALIGNANT ODONTOGENIC TUMORS. Alexandria Dental Journal, 44(3), 99-105. doi: 10.21608/adjalexu.2019.63566
Amal M. Sobhy; Hamed M.A. Fouad; Sahar M. Riad; Ibrahim M. Zaitoun. "EVALUATION OF SOX2 AS A POTENTIAL STEM CELL MARKER IN BENIGN AND MALIGNANT ODONTOGENIC TUMORS". Alexandria Dental Journal, 44, 3, 2019, 99-105. doi: 10.21608/adjalexu.2019.63566
Sobhy, A., Fouad, H., Riad, S., Zaitoun, I. (2019). 'EVALUATION OF SOX2 AS A POTENTIAL STEM CELL MARKER IN BENIGN AND MALIGNANT ODONTOGENIC TUMORS', Alexandria Dental Journal, 44(3), pp. 99-105. doi: 10.21608/adjalexu.2019.63566
Sobhy, A., Fouad, H., Riad, S., Zaitoun, I. EVALUATION OF SOX2 AS A POTENTIAL STEM CELL MARKER IN BENIGN AND MALIGNANT ODONTOGENIC TUMORS. Alexandria Dental Journal, 2019; 44(3): 99-105. doi: 10.21608/adjalexu.2019.63566
EVALUATION OF SOX2 AS A POTENTIAL STEM CELL MARKER IN BENIGN AND MALIGNANT ODONTOGENIC TUMORS
1Dentist at Alexandria Police Hospital, Alexandria, Egypt
2Professor of Oral Pathology Department, Faculty of Dentistry, Alexandria University
3Professor in Cranio-Maxillofacial and Plastic Surgery, Faculty of Dentistry, Alexandria University
Abstract
INTRODUCTION: Odontogenic tumors (OTs) constitute a wide range of lesions derived from the tooth forming apparatus and its remnants. These tumors are generally benign, yet some are aggressive and have locally invasive behavior with a high rate of recurrence and some are malignant. Tumor stem cells (TSCs) are a unique subpopulation of cells that possess the ability to initiate a neoplasm and sustain self-renewal. Epithelial stem cell (ESC) markers such as sex-determining region Y (SRY)-box 2 (SOX2) are capable of identifying these stem cells which are expressed during the early stages of tooth development. OBJECTIVES: To evaluate immunohistochemically the expression of the stem cell proliferating marker SOX2 in benign and malignant epithelial odontogenic tumors. MATERIAL AND METHODS: Immunohistochemical (IHC) study using the SOX2 antibody was done on 30 surgical specimens of benign and malignant epithelial OTs as study group and 5 normal tooth germ tissues as a control group. RESULTS: Malignant OTs biopsies showed intense immune-reactivity to SOX2, while aggressive benign OTs showed medium immunereactivity with variable intensity. Totally benign tumors were immune-negative. The IHC staining intensity was directly proportional to the state of malignancy of odontogenic tumors. The difference in the expression of SOX2 in malignant and benign OTs was statistically significant. However, the difference in the expression of SOX2 in OTs and control group was not statistically significant in mean of area percent, while it was statistically significant in mean of optical density. CONCLUSIONS: SOX2 is highly expressed in malignant OTs biopsies. Medium immune-reactivity with variable intensities is seen in aggressive benign OTs.
Ochsenius G, Ortega A, Godoy L, Penafiel C, Escobar E. Odontogenic tumors in Chile: a study of 362 cases. J Oral Pathol Med. 2002; 31:415-20.
Fernandes AM, Duarte EC, Pimenta EJ, Souza L, Santos V, Souza L, et al. Odontogenic tumors: a study of 340 cases in Brazilian population. J Oral Pathol Med. 2005; 34:583-7.
Kramer IRH, Pindborg JJ, Shear M. WHO histological typing of odontogenic tumors. 2nd ed. Berlin: Springer; 1992. p 11-27.
Scuibba JJ, Fantasia JE, Kahn LB. Tumors and cysts of the jaw. Washington DC: Atlas of tumor pathology, 3rd series, Armed Forces Institute of Pathology; 2001. p 71-99.
Leon Banes, John W, Eveson, Peter Reichart, Sidransky D. Pathology and genetics of head and neck tumors. In: Paul Kleihues MD, Leslie H. Sobin MD (eds). Lyon: IARC Press International Agency for Research on Cancer (IARC) 69008; 2005.
McClatchy KD. Tumors of the dental lamina: A selective review. Semin Diagn Pathol. 1987; 4:200-4.
Simpson HE. The degeneration of the rests of malassez with age as observed by apoxestic technique. J Periodontal. 1965; 36:288-91.
Nery EB, Kraus BS, Croup M. Timing and topography of early human tooth development. Arch Oral Biol. 1970;15:1315-26.
Mjor LA, Fejerskov O. Histology of the human tooth. 2nd ed. Copenhagen: Munksgaard; 1979.
Norberg O. Studies of the human jaws and teeth. Z Anat Entwicklungsgesch. 1960; 122:1-21.
El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ. WHO classification of head and neck tumours. 4th ed. 2017. P 204–60.
Avilion AA, Nicolis SK, Pevny LH, Perez L, Vivian N, Lovell-Badge R. Multipotent cell lineages in early mouse development depend on SOX2 function. Genes Dev. 2003; 17:126–40.
Mitsui K, Tokuzawa Y, Itoh H, Segawa K, Murakami M, Takahashi K, et al. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell. 2003; 113:631–42.
Ferletta M, Caglayan D, Mokvist L, Jiang Y, Kastemar M, Uhrbom L, et al. Forced expression of Sox21 inhibits Sox2 and induces apoptosis in human glioma cells. Int J Cancer. 2011; 129:45–60.
Han J, Zhang F, Yu M, Zhao P, Ji W, Zhang H, et al. RNA interference-mediated silencing of NANOG reduces cell proliferation and induces G0/G1 cell cycle arrest in breast cancer cells. Cancer Lett. 2012; 321:80–8.
Leis O, Eguiara A, Lopez-Arribillaga E, Alberdi MJ, Hernandez-Garcia S, Elorriaga K, et al. Sox2 expression in breast tumours and activation in breast cancer stem cells. Oncogene. 2012; 31:1354–65.
Jeter CR, Liu B, Liu X, Chen X, Liu C, Calhoun-Davis T, et al. NANOG promotes cancer stem cell characteristics and prostate cancer resistance to androgen deprivation. Oncogene. 2011; 30:3833–45.
Lazarus K, Hadi F, Zambon E, Bach K, Santolla MF, Watson JK, et al. PO-086 BCL11A interacts with SOX2 to control the expression of epigenetic regulators in lung squamous cell carcinoma. Nat Commun. 2018; 9:3327.
Talebi A, Kianersi K, Beiraghdar M. Comparison of gene expression of SOX2 and OCT4 in normal tissue, polyps, and colon adenocarcinoma using immunohistochemical staining. Adv Biomed Res. 2015; 4:234.
Lengerke C, Fehm T, Kurth R, Neubauer H, Scheble V, Müller F, et al. Expression of the embryonic stem cell marker SOX2 in early-stage breast carcinoma. BMC Cancer. 2011; 11:42.
Kim BW, Cho H, Choi CH, Ylaya K, Chung JY, Kim JH, et al. Clinical significance of OCT4 and SOX2 protein expression in cervical cancer. BMC Cancer. 2015; 15:1015.
Sanada Y, Yoshida K, Ohara M, Oeda M, Konishi K, Tsutani Y. Histopathologic evaluation of stepwise progression of pancreatic carcinoma with immunohistochernical analysis of gastric epithelial transcription factor SOX2 - Comparison of expression patterns between invasive components and cancerous or nonneoplastic intraductal components. Pancreas. 2006,32:164-70.
Mosqueda-Taylor A, Menesses GA, Ruiz Gody LM, Suarez RM, Luna O. Malignant odontogenic tumors. A retrospective study of 7 cases. Med Oral. 2003; 8:110-21.
Kero D, Novakovic J, Vukojevic K, Petricevic J, Kalibovic Govorko D, Biocina-Lukenda D, et al. Expression of Ki67, Oct-4, γ-tubulin and α-tubulin in human tooth development. Arch Oral Bio. 2014; 59:1119-29.
Juuri E, Isaksson S, Jussila M, Heikinheimo K, Thesleff I. Expression of the stem cell marker, SOX2, in ameloblastoma and dental epithelium. Eur J Oral Sci. 2013; 121:509–16.
Qiao B, He B, Cai J, Yang W. The expression profile of Oct 4 and Sox2 in the carcinogenesis of oral mucosa. Int J Clin Exp Pathol. 2014;7:28-37.
Sandra F, Nakamura N, Mitsuyasu T, Shiratsuchi Y, Ohishi M. Two relativity distinct patterns of ameloblastoma: an anti-apoptotic proliferating site in the outer layer (periphery) and a pro-apoptotic differentiating site in the inner layer (center). Histopathology. 2001; 39:93-8.
Chiou SH, Wang ML, Chou YT, Chen CJ, Hong CF, Hsieh WJ, et al. Coexpression of Oct4 and nanog enhances malignancy in lung adenocarcinoma by inducing cancer stem cell–likeproperties and epithelial–mesenchymal transdifferentiation. Cancer Res. 2010; 70:10433-44.
Lei Y, Jaradat JM, Owosho A, Adebiyi KE, Lybrand KS, Neville BW, et al. Evaluation of SOX2 as a potential marker for ameloblastic carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol. 2014; 117:608-16.e1.
Bass AJ, Watanabe H, Mermel CH, Yu S, Perner S, Verhaak RG, et al. SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas. Nat Genet. 2009; 41:1238–42.
Freier K, Knoepfle K, Flechtenmacher C, Pungs S, Devens F, Toedt G, et al. Recurrent copy number gain of transcription factor SOX2 and corresponding high protein expression in oral squamous cell carcinoma. Genes Chromosom Cancer. 2010; 49:9–16.
Schepers AG, Snippert HJ, Stange DE, van den Born M, van Es JH, van de Wetering M, et al. Lineage tracing reveals lgr5+ stem cell activity in mouse intestinal adenomas. Science. 2012; 337:730–5.
Da Silva-Diz V, Solé-Sánchez S, Valdés-Gutiérrez A, Urpí M, Riba-Artés D, Penin RM, Progeny of lgr5-expressing hair follicle stem cell contributes to papillomavirusinduced tumor development in epidermis. Oncogene. 2013; 32:3732–43.
Mary S, Muller S. Malignant Odontogenic Tumors: An Update on Selected Tumors. Head and Neck Pathol. 2014; 8:411–20.
Woolgar JA, Triantafyllou A, Ferlito A, Devaney KO, Lewis JS Jr, Rinaldo A, et al. Intraosseous carcinoma of the jaws: a clinicopathologic review, part II: odontogenic carcinomas. Head Neck. 2013; 35:902-5.
Barnes L, Eveson J, Reichart P, Sidransky D. World Health Organization classification of tumours: pathology and genetics of head and neck tumours. Lyon: IARC Press; 2005. p 284–91.
Hall JM, Weathers DR, Krishnan K. Ameloblastic carcinoma: an analysis of 14 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endodontol. 2007; 103:799–807.
Yoon H-J, Hong S-P, Lee J-I. Ameloblastic carcinoma: an analysis of 6 cases with review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endodontol. 2009;108:904–13.
Banerjee A, Kamath VV, Sundaram L, Krishnamurthy SS. OCT4 and SOX2 are reliable markers in detecting stem cells in odontogenic lesions. J Orofac Sci. 2016; 8:16-21.