Stem Cell Markers SOX-2 and OCT-4 Enable to Resolve the Diagnostic Dilemma between Ameloblastic Carcinoma and Aggressive Solid Multicystic Ameloblastoma

Khan, Wafa; Augustine, Dominic; Rao, Roopa S; Venkatesiah Sowmya, Samudrala; Haragannavar, Vanishri C; Nambiar, Shwetha

Stem Cell Markers SOX-2 and OCT-4 Enable to Resolve the Diagnostic Dilemma between Ameloblastic Carcinoma and Aggressive Solid Multicystic Ameloblastoma

Document Type : Original Article

Authors

Department of Oral Pathology and Microbiology, Faculty of Dental Sciences, M.S. Ramaiah University of Applied Sciences, Bengaluru, Karnataka, India

Abstract

Background: Ameloblastic carcinoma (ACA) is a malignant neoplasm with overlapping histopathological features of benign aggressive solid multicystic ameloblastoma (SMA). This often leads to misdiagnosis with direct implication on the management protocol. The need of the hour is to adopt reliable tissue biomarkers to differentiate these lesions accurately that will help to implement an appropriate treatment modality. Few studies to differentiate ACA and SMA in literature with a limitation of a single marker and lack of availability of cases have prompted us to undertake this study. Thereby, this study is aimed at resolving the diagnostic dilemma in differentiating ACA and aggressive SMA using SOX-2, OCT-4 and CD44. Materials and Methods: Tissue samples involved 40 archival cases of histopathologically confirmed cases of ACA (n = 20) and SMA (n = 20). The sections were subjected to immunohistochemical staining using antibodies to SOX-2, OCT-4 and CD44. Nuclear staining for SOX-2 and OCT-4 and membranous reactivity for CD44 was considered positive. Results: The expression of SOX-2 and OCT-4 in ACA was statistically significant when compared to SMA (P < 0.001). CD44 showed an insignificant statistical value of <0.077 in differentiating ACA and SMA. SOX-2 and OCT-4 expression in ACA showed a significant correlation coefficient of 0.616 at P < 0.004. Conclusions: SOX-2 and OCT-4 could serve as independent novel markers in resolving the diagnostic dilemma between ACA and aggressive SMA.

Keywords

References

1.	Slater LJ. Odontogenic malignancies. Oral Maxillofac Surg Clin North Am 2004;16:409-24.
2.	Jiang C, Xu Q, Zhang Q, Wang S, Carrasco LR, Le AD. Benign odontogenic tumors: Origins, immunophenotypic features, and genetic alterations. Curr Oral Health Rep 2016;3:93-101.
3.	Benlyazid A, Lacroix-Triki M, Aziza R, Gomez-Brouchet A, Guichard M, Sarini J. Ameloblastic carcinoma of the maxilla: Case report and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;104:e17-24.
4.	Yoon HJ, Hong SP, Lee JI, Lee SS, Hong SD. Ameloblastic carcinoma: An analysis of 6 cases with review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;108:904-13.
5.	Cheng L, Alexander R, Zhang S, Pan CX, MacLennan GT, Lopez-Beltran A, et al. The clinical and therapeutic implications of cancer stem cell biology. Expert Rev Anticancer Ther 2011;11:1131-43.
6.	Ge N, Lin HX, Xiao XS, Guo L, Xu HM, Wang X, et al. Prognostic significance of Oct4 and So×2 expression in hypopharyngeal squamous cell carcinoma. J Transl Med 2010;8:94.
7.	Srinath S, Iyengar A, Mysorekar V. CD 44 expression in dentigerous cyst, radicular cyst and ameloblastoma, by immunohistochemical analysis. IOSR J Dent Med Sci 2014;13:80-3.
8.	Imran A, Jayanthi P, Tanveer S, Gobu SC. Classification of odontogenic cysts and tumors – Antecedents. J Oral Maxillofac Pathol 2016;20:269-71. [PUBMED] [Full text]
9.	Kumaran PS, Anuradha V, Gokkulakrishnan S, Thambiah L, Jagadish AK, Satheesh G. Ameloblastic carcinoma: A case series. J Pharm Bioallied Sci 2014;6:S208-11.
10.	Reichart PA, Philipsen HP. Odontogenic Tumors and Allied Lesions. Hanover, Germany: Quintessence Publishing; 2004.
11.	Hunter KD, Speight PM. The diagnostic usefulness of immunohistochemistry for odontogenic lesions. Head Neck Pathol 2014;8:392-9.
12.	Luo W, Li S, Peng B, Ye Y, Deng X, Yao K. Embryonic stem cells markers SOX2, OCT4 and Nanog expression and their correlations with epithelial-mesenchymal transition in nasopharyngeal carcinoma. PLoS One 2013;8:e56324.
13.	Hussenet T, Dali S, Exinger J, Monga B, Jost B, Dembelé D, et al. SOX2 is an oncogene activated by recurrent 3q26.3 amplifications in human lung squamous cell carcinomas. PLoS One 2010;5:e8960.
14.	Juuri E, Saito K, Ahtiainen L, Seidel K, Tummers M, Hochedlinger K, et al. Sox2+ stem cells contribute to all epithelial lineages of the tooth via Sfrp5+ progenitors. Dev Cell 2012;23:317-28.
15.	Juuri E, Jussila M, Seidel K, Holmes S, Wu P, Richman J, et al. Sox2 marks epithelial competence to generate teeth in mammals and reptiles. Development 2013;140:1424-32.
16.	Zeineddine D, Hammoud AA, Mortada M, Boeuf H. The Oct4 protein: More than a magic stemness marker. Am J Stem Cells 2014;3:74-82.
17.	Niwa H, Miyazaki J, Smith AG. Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat Genet 2000;24:372-6.
18.	Hochedlinger K, Yamada Y, Beard C, Jaenisch R. Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues. Cell 2005;121:465-77.
19.	Jiang WG, Sanders AJ, Katoh M, Ungefroren H, Gieseler F, Prince M, et al. Tissue invasion and metastasis: Molecular, biological and clinical perspectives Semin Cancer Biol. 2015 Dec;35 Suppl:S244-S275. doi: 10.1016/j.semcancer.2015.03.008. Epub 2015 Apr 10.
20.	Mao M, Zheng X, Jin B, Zhang F, Zhu L, Cui L. Effects of CD44 and E-cadherin overexpression on the proliferation, adhesion and invasion of ovarian cancer cells. Exp Ther Med 2017;14:5557-63.
21.	Basakran NS. CD44 as a potential diagnostic tumor marker. Saudi Med J 2015;36:273-9.
22.	Olsson E, Honeth G, Bendahl PO, Saal LH, Gruvberger-Saal S, Ringnér M, et al. CD44 isoforms are heterogeneously expressed in breast cancer and correlate with tumor subtypes and cancer stem cell markers. BMC Cancer 2011;11:418.
23.	Fan Z, Li M, Chen X, Wang J, Liang X, Wang H, et al. Prognostic value of cancer stem cell markers in head and neck squamous cell carcinoma: A meta-analysis. Sci Rep 2017;7:43008.
24.	Martínez-Martínez M, Mosqueda-Taylor A, Carlos-Bregni R, Pires FR, Delgado-Azanero W, Neves-Silva R, et al. Comparative histological and immunohistochemical study of ameloblastomas and ameloblastic carcinomas. Med Oral Patol Oral Cir Bucal 2017;22:e324-32.
25.	Loyola AM, Cardoso SV, de Faria PR, Servato JP, Eisenberg AL, Dias FL, et al. Ameloblastic carcinoma: A Brazilian collaborative study of 17 cases. Histopathology 2016;69:687-701.
26.	Yoon HJ, Jo BC, Shin WJ, Cho YA, Lee JI, Hong SP, et al. Comparative immunohistochemical study of ameloblastoma and ameloblastic carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011;112:767-76.
27.	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. [Full text]
28.	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;117:608-160.
29.	Bandyopadhyay A, Nishat R, Behura SS, Panda A, Ramachandra S, Mohiddin G. Cancer stem cell markers, SO×2 and OCT 4 in ameloblastoma and keratocystic odontogenic tumor: An immunohistochemical study. J Int Oral Health 2017;9:28-32. [Full text]
30.	Reers S, Pfannerstill AC, Maushagen R, Pries R, Wollenberg B. Stem cell profiling in head and neck cancer reveals an Oct-4 expressing subpopulation with properties of chemoresistance. Oral Oncol 2014;50:155-62.
31.	Sathi GA, Tamamura R, Tsujigiwa H, Katase N, Lefeuvre M, Siar CH, et al. Analysis of immunoexpression of common cancer stem cell markers in ameloblastoma. Exp Ther Med 2012;3:397-402.
32.	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.

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