{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T04:57:01Z","timestamp":1775883421414,"version":"3.50.1"},"reference-count":83,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013272","name":"The Health Programme","doi-asserted-by":"crossref","award":["351058"],"award-info":[{"award-number":["351058"]}],"id":[{"id":"10.13039\/100013272","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Background: Malignant salivary gland tumors represent a highly diverse group of neoplasms, their heterogeneity likely arising due to variable origin in different tissue components. Emerging evidence suggests that SOX-2 and EZH-2 play critical roles in salivary gland carcinogenesis, being related to tumor cell stemness potential, along with accelerated tumor progression and unfavorable clinical outcomes. The aim of this study was to assess the association between SOX-2 and EZH-2 expression, survival parameters, and tumors\u2019 pathological characteristics in a group of patients with primary epithelial malignant salivary gland tumors (MSGTs) and to evaluate their value as diagnostic and prognostic markers. Methods: Our study group comprised 104 patients with primary epithelial MSGTs diagnosed in \u201cSf. Spiridon\u201d County Hospital, Iasi, over a period of fifteen years. Pathological parameters and survival evaluation, along with SOX-2 and EZH-2 immunohistochemistry assessment and scoring, were conducted, and the associations between different parameters were analyzed. Results: High SOX-2 immunoexpression was significantly associated with lymphatic invasion (LY) (p = 0.003), pT stage (p = 0.010), histological tumor type (p = 0.003), and tumor grading (p = 0.037), while high EZH-2 immunoexpression was significantly associated with perineural invasion (PnI) (p &lt; 0.001), vascular invasion (p = 0.038), LY (p = 0.001), tumor grading (p = 0.002), and pathological extranodal extension (pENE) (p = 0.018). The tumors with high SOX-2 and EZH-2 expressions were associated with a reduced overall survival (OS) (p = 0.013 and p = 0.011). Cox regression analysis revealed that pT (HR = 1.826, p = 0.019), LY (HR = 0.318, p = 0.007), and tumor grade (HR = 0.505, p = 0.021) added to high SOX-2 and EZH-2 immunoexpression independently predicted a poor survival outcome (HR = 2.373, p = 0.016 and HR = 2.746, p = 0.015). Conclusions: Our findings suggest that SOX-2 and EZH-2 may serve as biomarkers of aggressive behavior and a poor prognosis in primary epithelial MSGTs, providing potential opportunities for precision-targeted therapies.<\/jats:p>","DOI":"10.3390\/medsci14020188","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T08:56:07Z","timestamp":1775724967000},"page":"188","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["SOX-2 and EZH-2 Expression in Primary Epithelial Malignant Salivary Gland Tumors"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4356-4957","authenticated-orcid":false,"given":"Constantin Aleodor","family":"Costin","sequence":"first","affiliation":[{"name":"Department of Morphofunctional Sciences I, Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Ia\u0219i, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6641-5135","authenticated-orcid":false,"given":"Adriana","family":"Grigora\u0219","sequence":"additional","affiliation":[{"name":"Department of Morphofunctional Sciences I, Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Ia\u0219i, Romania"},{"name":"Institute of Legal Medicine Iasi, 700455 Ia\u0219i, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8228-104X","authenticated-orcid":false,"given":"Cornelia","family":"Amalinei","sequence":"additional","affiliation":[{"name":"Department of Morphofunctional Sciences I, Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Ia\u0219i, Romania"},{"name":"Institute of Legal Medicine Iasi, 700455 Ia\u0219i, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"ref_1","first-page":"201","article-title":"Molecular Landscape of Salivary Gland Malignancies. What Is Already Known?","volume":"28","author":"Pikul","year":"2024","journal-title":"Contemp. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"100602","DOI":"10.1016\/j.esmoop.2022.100602","article-title":"Salivary gland cancer: ESMO-European Reference Network on Rare Adult Solid Cancers (EURACAN) Clinical Practice Guideline for diagnosis, treatment and follow-up","volume":"7","author":"Poorten","year":"2022","journal-title":"ESMO Open"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1177\/23202068241229302","article-title":"Incidence and Mortality of Salivary Gland Cancer Worldwide and Its Correlation with Tobacco Use (Smoking and Chewing) and with the Human Development Index","volume":"15","author":"Ortiz","year":"2024","journal-title":"J. Adv. Oral Res."},{"key":"ref_4","first-page":"597","article-title":"The Evolving Landscape of Salivary Gland Tumors","volume":"73","author":"Steuer","year":"2023","journal-title":"CA Cancer J. Clin."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Gontarz, M., Bargiel, J., Gasiorowski, K., Marecik, T., Szczurowski, P., Zapa\u0142a, J., and Wyszy\u2019nska-Pawelec, G. (2021). Epidemiology of Primary Epithelial Salivary Gland Tumors in Southern Poland\u2014A 26-Year, Clinicopathologic, Retrospective Analysis. J. Clin. Med., 10.","DOI":"10.3390\/jcm10081663"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"8393","DOI":"10.3390\/ijms15058393","article-title":"High Expression of SOX2 Is Associated with Poor Prognosis in Patients with Salivary Gland Adenoid Cystic Carcinoma","volume":"15","author":"Dai","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"113860","DOI":"10.1016\/j.biopha.2022.113860","article-title":"SOX2 Function in Cancers: Association with Growth, Invasion, Stemness and Therapy Response","volume":"156","author":"Mirzaei","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"114336","DOI":"10.1016\/j.biopha.2023.114336","article-title":"SOX2-Associated Signaling Pathways Regulate Biological Phenotypes of Cancers","volume":"160","author":"Ding","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e26620","DOI":"10.7554\/eLife.26620","article-title":"SOX2 Regulates Acinar Cell Development in the Salivary Gland","volume":"6","author":"Emmerson","year":"2017","journal-title":"eLife"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"103508","DOI":"10.1016\/j.isci.2021.103508","article-title":"A Mechanistic Basis for the Malignant Progression of Salivary Gland Tumors","volume":"24","author":"Taniguchi","year":"2021","journal-title":"iScience"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1369\/0022155415590829","article-title":"Silencing SOX2 Expression by RNA Interference Inhibits Proliferation, Invasion and Metastasis, and Induces Apoptosis through MAP4K4\/JNK Signaling Pathway in Human Laryngeal Cancer TU212 Cells","volume":"63","author":"Yang","year":"2015","journal-title":"J. Histochem. Cytochem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/s41392-020-00242-3","article-title":"Functional Characterization of SOX2 as an Anticancer Target","volume":"5","author":"Zhang","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1007\/s00428-017-2220-1","article-title":"Increased SOX2 Expression in Salivary Gland Carcinoma Ex Pleomorphic Adenoma Progression: An Association with Adverse Outcome","volume":"471","author":"Sedassari","year":"2017","journal-title":"Virchows Arch."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e018","DOI":"10.1590\/1807-3107bor-2024.vol38.0018","article-title":"EZH2 immunoexpression in pleomorphic adenoma and adenoid cystic carcinoma and clinicopathological features","volume":"38","author":"Viana","year":"2024","journal-title":"Braz. Oral Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1111\/cas.14840","article-title":"The Noncanonical Role of EZH2 in Cancer","volume":"112","author":"Huang","year":"2021","journal-title":"Cancer Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e20250123","DOI":"10.1590\/1678-7757-2025-0123","article-title":"EZH2 Expression Is Restricted to Malignant Salivary Gland Tumors","volume":"33","author":"Bumalee","year":"2025","journal-title":"J. Appl. Oral Sci."},{"key":"ref_17","first-page":"16","article-title":"Screening and Identification of Gene Expression in Large Cohorts of Clinical Tissue Samples Unveils the Major Involvement of EZH2 and SOX2 in Lung Cancer","volume":"290\u2013291","author":"Sadhukhan","year":"2025","journal-title":"Cancer Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1093\/carcin\/bgv064","article-title":"Survival of Skin Cancer Stem Cells Requires the Ezh2 Polycomb Group Protein","volume":"36","author":"Adhikary","year":"2015","journal-title":"Carcinogenesis"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s13148-024-01666-2","article-title":"Polycomb Repressive Complex 2 and Its Core Component EZH2: Potential Targeted Therapeutic Strategies for Head and Neck Squamous Cell Carcinoma","volume":"16","author":"Cheng","year":"2024","journal-title":"Clin. Epigenetics"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1136\/jcp.2007.054262","article-title":"High Expression of Polycomb Group Protein EZH2 Predicts Poor Survival in Salivary Gland Adenoid Cystic Carcinoma","volume":"61","author":"Raaphorst","year":"2008","journal-title":"J. Clin. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Saigusa, N., Hirai, H., Tada, Y., Kawakita, D., Nakaguro, M., Tsukahara, K., Kano, S., Ozawa, H., Kondo, T., and Okami, K. (2022). The Role of the EZH2 and H3K27me3 Expression as a Predictor of Clinical Outcomes in Salivary Duct Carcinoma Patients: A Large-Series Study With Emphasis on the Relevance to the Combined Androgen Blockade and HER2-Targeted Therapy. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.779882"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Campolo, M., Scuderi, S.A., Filippone, A., Bova, V., Lombardo, S.P., Colarossi, L., Sava, S., Capra, A.P., De Gaetano, F., and Portelli, M. (2024). EZH2 Inhibition to Counteract Oral Cancer Progression through Wnt\/\u03b2-Catenin Pathway Modulation. Pharmaceuticals, 17.","DOI":"10.3390\/ph17081102"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.jds.2016.12.002","article-title":"The Association of Betel Quid, Alcohol, and Cigarettes with Salivary Gland Tumor\u2014A Case\u2013Control Study","volume":"12","author":"Li","year":"2017","journal-title":"J. Dent. Sci."},{"key":"ref_24","unstructured":"WHO (2024). Classification of Tumours Head and Neck Tumours."},{"key":"ref_25","unstructured":"Asare, E. (2025). Vander Poorten Vincent AJCC Cancer Staging System: Salivary Gland, American College of Surgeons. [9th ed.]."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Zhang, L., Deng, Y., Liu, S., Zhang, W., Hong, Z., Lu, Z., Pan, Z., Wu, X., and Peng, J. (2023). Lymphovascular Invasion Represents a Superior Prognostic and Predictive Pathological Factor of the Duration of Adjuvant Chemotherapy for Stage III Colon Cancer Patients. BMC Cancer, 23.","DOI":"10.1186\/s12885-022-10416-7"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1186\/s13000-015-0392-z","article-title":"EZH2 Is a Sensitive Marker of Malignancy in Salivary Gland Tumors","volume":"10","author":"Vincze","year":"2015","journal-title":"Diagn. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s13000-016-0491-5","article-title":"EZH2 Overexpression in Different Immunophenotypes of Breast Carcinoma and Association with Clinicopathologic Features","volume":"11","author":"Guo","year":"2016","journal-title":"Diagn. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1111\/cdoe.13033","article-title":"Global Epidemiology and Socioeconomic Correlates of Salivary Gland Cancer from 2020 to 2040","volume":"53","author":"Mousavi","year":"2025","journal-title":"Community Dent. Oral Epidemiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1007\/s12105-022-01459-0","article-title":"Distribution and Frequency of Salivary Gland Tumours: An International Multicenter Study","volume":"16","author":"Alsanie","year":"2022","journal-title":"Head Neck Pathol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1002\/cncr.30957","article-title":"Heterogeneous Impact of Smoking on Major Salivary Gland Cancer According to Histopathological Subtype: A Case-control Study","volume":"124","author":"Sawabe","year":"2018","journal-title":"Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"395","DOI":"10.47162\/RJME.65.3.02","article-title":"Are HPV oncogenic viruses involved in salivary glands tumorigenesis?","volume":"65","author":"Costin","year":"2024","journal-title":"Rom. J. Morphol. Embryol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"112","DOI":"10.18332\/tid\/189303","article-title":"Oral Squamous Cell Carcinoma: Effect of Tobacco and Alcohol on Cancer Location","volume":"22","author":"Eloranta","year":"2024","journal-title":"Tob. Induc. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Grigoras, A., and Amalinei, C. (2025). The Role of Perirenal Adipose Tissue in Carcinogenesis\u2014From Molecular Mechanism to Therapeutic Perspectives. Cancers, 17.","DOI":"10.3390\/cancers17071077"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Grigoras, A., and Amalinei, C. (2023). Multi-Faceted Role of Cancer-Associated Adipocytes in Colorectal Cancer. Biomedicines, 11.","DOI":"10.3390\/biomedicines11092401"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1093\/aje\/kwh041","article-title":"Association of Obesity and Cancer Risk in Canada","volume":"159","author":"Pan","year":"2004","journal-title":"Am. J. Epidemiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1080\/01635580802143851","article-title":"Salivary Gland Cancer: An Exploratory Analysis of Dietary Factors","volume":"60","author":"Forrest","year":"2008","journal-title":"Nutr. Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1017\/S002221512200007X","article-title":"Twenty-Seven Years of Primary Salivary Gland Carcinoma in Wales: An Analysis of Histological Subtype and Associated Risk Factors","volume":"136","author":"Leopard","year":"2022","journal-title":"J. Laryngol. Otol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Costin, C.A., Grigoras, A., Andriescu, E.C., and Amalinei, C. (2025). Benign Epithelial Salivary Neoplasms: Single-Centered Histopathologic and Clinicodemographic Romanian Retrospective Study. Clin. Pract., 15.","DOI":"10.3390\/clinpract15120235"},{"key":"ref_40","first-page":"141","article-title":"Indications for Salivary Gland Radiotherapy","volume":"78","author":"Thomson","year":"2016","journal-title":"Adv. Otorhinolaryngol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1002\/cncr.32792","article-title":"Distant Metastasis of Salivary Gland Cancer: Incidence, Management, and Outcomes","volume":"126","author":"Mimica","year":"2020","journal-title":"Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"105076","DOI":"10.1016\/j.oraloncology.2020.105076","article-title":"The Impact of Nodal Status in Major Salivary Gland Carcinoma: A Multicenter Experience and Proposal of a Novel N-Classification","volume":"112","author":"Lombardi","year":"2021","journal-title":"Oral Oncol."},{"key":"ref_43","unstructured":"Young, A., and Okuyemi, O.T. (2023). Malignant Salivary Gland Tumors, StatPearls Publishing LLC."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Liu, F., Chu, Y., Zheng, Q., Hu, Y., Wang, Y., Qin, L., Fu, S., and Wang, S. (2025). Major and Minor Perineural Invasion in Salivary Gland Cancer. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1466196"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"116196","DOI":"10.1016\/j.ejca.2025.116196","article-title":"Incidence and Survival of Primary Major Salivary Gland Carcinoma in Germany over the Last Decade: A Nationwide Population-Based Study","volume":"234","author":"Jansen","year":"2026","journal-title":"Eur. J. Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"100523","DOI":"10.1016\/j.adoms.2025.100523","article-title":"Comprehensive Five-Year Study on Salivary Gland Tumors: Demographic, Clinical, and Histopathological Insights","volume":"17","author":"Rajbhar","year":"2025","journal-title":"Adv. Oral Maxillofac. Surg."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1016\/j.ejso.2023.04.002","article-title":"Association between Factor of Parotid Lymph Node and Prognosis in Parotid Cancer","volume":"49","author":"Fang","year":"2023","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"107131","DOI":"10.1016\/j.oraloncology.2024.107131","article-title":"Predictors of Recurrence and Survival after Salivary Gland Cancer Surgery: A Multicenter, Retrospective Study in Northern Japan","volume":"160","author":"Ohkoshi","year":"2025","journal-title":"Oral Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1177\/0194599817751888","article-title":"Perineural Invasion in Parotid Gland Malignancies","volume":"158","author":"Huyett","year":"2018","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"105937","DOI":"10.1016\/j.oraloncology.2022.105937","article-title":"The Role of Perineural Invasion in Parotid Malignancy Outcomes: A Systematic Review and Meta-Analysis","volume":"130","author":"Kazemian","year":"2022","journal-title":"Oral Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1111\/his.12488","article-title":"Prognostic Features in Mucoepidermoid Carcinoma of Major Salivary Glands with Emphasis on Tumour Histologic Grading","volume":"65","author":"Katabi","year":"2014","journal-title":"Histopathology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.ijom.2019.11.007","article-title":"Prognostic significance of lymphovascular invasion in patients with salivary duct cell carcinoma of the head and neck","volume":"49","author":"Park","year":"2020","journal-title":"Int. J. Oral Maxillofac. Surg."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1002\/jso.23874","article-title":"Prognostic Value of Lymph Node Density in High-grade Salivary Gland Cancers","volume":"111","author":"Hong","year":"2015","journal-title":"J. Surg. Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1002\/jso.23914","article-title":"Patterns and Treatment of Neck Metastases in Patients with Salivary Gland Cancers","volume":"111","author":"Yoo","year":"2015","journal-title":"J. Surg. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.1002\/hed.26135","article-title":"Positive Lymph Node Number and Extranodal Extension for Predicting Recurrence and Survival in Patients with Salivary Gland Cancer","volume":"42","author":"Lee","year":"2020","journal-title":"Head Neck"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1016\/j.joms.2024.06.179","article-title":"The Number of Positive Lymph Nodes Instead of Extranodal Extension and Nodal Diameter Is an Independent Predictor of Survival and Treatment Outcome of High-Grade Parotid Gland Carcinoma","volume":"82","author":"Brajkovic","year":"2024","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"S109","DOI":"10.14639\/0392-100X-suppl.1-45-2025-N1108","article-title":"Margins in Major Salivary Gland Surgery: Clinical and Pathological Criteria for Defining Margins and Their Implications on the Choice of Multimodal Therapies. A Systematic Review","volume":"45","author":"Pagliuca","year":"2025","journal-title":"Acta Otorhinolaryngol. Ital."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1001\/jamaoto.2021.3459","article-title":"Evaluation of Surgical Margin Status in Patients With Salivary Gland Cancer","volume":"148","author":"Hanson","year":"2022","journal-title":"JAMA Otolaryngol. Head Neck Surg."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"106484","DOI":"10.1016\/j.oraloncology.2023.106484","article-title":"Prognostic factors in surgically treated malignant salivary gland tumors","volume":"144","author":"Hofmann","year":"2023","journal-title":"Oral Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1002\/lio2.723","article-title":"Prognostic analysis and establishment of a nomogram in patients with myoepithelial carcinoma of the salivary gland: A population-based study","volume":"7","author":"Liu","year":"2022","journal-title":"Laryngoscope Investig. Otolaryngol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Kalogirou, E.-M., Tosiou, A., Vrachnos, S., Zogopoulos, V.L., Michalopoulos, I., Tzanavari, T., and Tosios, K.I. (2025). The Immunoexpression and Prognostic Significance of Stem Cell Markers in Malignant Salivary Gland Tumors: A Systematic Review and Meta-Analysis. Genes, 16.","DOI":"10.3390\/genes16010037"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1097\/PAI.0000000000001006","article-title":"Prognostic Significance of Cancer Stem Cell Markers in Patients With Salivary Gland Carcinomas","volume":"30","author":"Sadeghi","year":"2022","journal-title":"Appl. Immunohistochem. Mol. Morphol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.oooo.2022.09.038","article-title":"Immunohistochemical Comparative Analysis of Tumor Stem Cell Biomarkers in Pleomorphic Adenoma, Adenoid Cystic Carcinoma and Mucoepidermoid Carcinoma of Salivary Glands","volume":"135","author":"Mafra","year":"2023","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/j.jiph.2019.03.015","article-title":"Correlation between SOX2 and Survivin Clinical Features in Patients with Salivary Adenoid Cystic Carcinoma","volume":"12","author":"Luo","year":"2019","journal-title":"J. Infect. Public Health"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1007\/s00405-020-06389-7","article-title":"Cancer Stem Cell Markers in Adenocarcinoma of the Salivary Glands\u2014Reliable Prognostic Markers?","volume":"278","author":"Spiegel","year":"2021","journal-title":"Eur. Arch. Oto-Rhino-Laryngol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Thierauf, J., Weissinger, S.E., Veit, J.A., Affolter, A., Laureano, N.K., Beutner, D., Heiduschka, G., Kadletz, L., Meyer, M., and Quaas, A. (2018). Low SOX2 Expression Marks a Distinct Subset of Adenoid Cystic Carcinoma of the Head and Neck and Is Associated with an Advanced Tumor Stage. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0194989"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1159\/000514101","article-title":"Cancer Stem Cell Markers in Squamous Cell Carcinomas of the Salivary Glands","volume":"99","author":"Bertlich","year":"2021","journal-title":"Oncology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"43907","DOI":"10.1038\/srep43907","article-title":"Prognostic Factors of Palatal Mucoepidermoid Carcinoma: A Retrospective Analysis Based on a Double-Center Study","volume":"7","author":"Xu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"102526","DOI":"10.1016\/j.jormas.2025.102526","article-title":"Association of TP53 and EZH2 with Salivary Adenoid Cystic Carcinoma","volume":"126","author":"Di","year":"2025","journal-title":"J. Stomatol. Oral Maxillofac. Surg."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e14349","DOI":"10.7717\/peerj.14349","article-title":"Immunoexpression of Stem Cell Markers SOX-2, NANOG AND OCT4 in Ameloblastoma","volume":"11","author":"Balbinot","year":"2023","journal-title":"PeerJ"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"37974","DOI":"10.18632\/oncotarget.16467","article-title":"Role of EZH2 in Cancer Stem Cells: From Biological Insight to a Therapeutic Target","volume":"8","author":"Wen","year":"2017","journal-title":"Oncotarget"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Verma, S., Goyal, N., Goyal, S., Kaur, P., and Gupta, S. (2025). EZH2 Dysregulation and Its Oncogenic Role in Human Cancers. Cancers, 17.","DOI":"10.3390\/cancers17193111"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s12032-025-02648-x","article-title":"Exosomal RNAs and EZH2: Unraveling the Molecular Dialogue Driving Tumor Progression","volume":"42","author":"Zwamel","year":"2025","journal-title":"Med. Oncol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.canlet.2019.04.010","article-title":"Combined Class I Histone Deacetylase and MTORC1\/C2 Inhibition Suppresses the Initiation and Recurrence of Oral Squamous Cell Carcinomas by Repressing SOX2","volume":"454","author":"Liang","year":"2019","journal-title":"Cancer Lett."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1002\/cam4.2772","article-title":"EGFR Enhances the Stemness and Progression of Oral Cancer through Inhibiting Autophagic Degradation of SOX2","volume":"9","author":"Lv","year":"2020","journal-title":"Cancer Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3256","DOI":"10.1158\/1538-7445.AM2024-3256","article-title":"Abstract 3256: Novel SOX2-Targeting BioPROTACs for the Treatment of Cancers","volume":"84","author":"Choi","year":"2024","journal-title":"Cancer Res."},{"key":"ref_77","first-page":"1165","article-title":"Targeting of EZH2 Inhibits Epithelial Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma via Regulating the STAT3\/VEGFR2 Axis","volume":"55","author":"Zhao","year":"2019","journal-title":"Int. J. Oncol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Oppelt, P.J., Puram, S.V., Liu, J., Ley, J.C., and Adkins, D. (2025). Tazemetostat, a Selective EZH2 Inhibitor, in Combination with Pembrolizumab for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: A Phase 1 Trial. Cancers, 17.","DOI":"10.3390\/cancers17030437"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Migliorelli, A., Manuelli, M., Ciorba, A., Stomeo, F., Pelucchi, S., and Bianchini, C. (2025). The Role of Blood Inflammatory Markers in Salivary Gland Carcinoma: A Scoping Review. J. Clin. Med., 14.","DOI":"10.3390\/jcm14051762"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"19160216251364761","DOI":"10.1177\/19160216251364761","article-title":"Prognostic Significance of Neutrophil-Lymphocyte Ratio in Salivary Gland Neoplasms: A Systematic Review","volume":"54","author":"Zaidi","year":"2025","journal-title":"J. Otolaryngol. Head Neck Surg."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1177\/0194599816659257","article-title":"Pretreatment Neutrophil Lymphocyte Ratio in Salivary Gland Tumors Is Associated with Malignancy","volume":"155","author":"Damar","year":"2016","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Committeri, U., Barone, S., Salzano, G., Arena, A., Borriello, G., Giovacchini, F., Fusco, R., Vaira, L.A., Scarpa, A., and Abbate, V. (2023). Support Tools in the Differential Diagnosis of Salivary Gland Tumors through Inflammatory Biomarkers and Radiomics Metrics: A Preliminary Study. Cancers, 15.","DOI":"10.3390\/cancers15061876"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Abbate, V., Barone, S., Troise, S., Laface, C., Bonavolont\u00e0, P., Pacella, D., Salzano, G., Iaconetta, G., Califano, L., and Dell\u2019Aversana Orabona, G. (2022). The Combination of Inflammatory Biomarkers as Prognostic Indicator in Salivary Gland Malignancy. Cancers, 14.","DOI":"10.3390\/cancers14235934"}],"container-title":["Medical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3271\/14\/2\/188\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T04:28:52Z","timestamp":1775881732000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3271\/14\/2\/188"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,9]]},"references-count":83,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["medsci14020188"],"URL":"https:\/\/doi.org\/10.3390\/medsci14020188","relation":{},"ISSN":["2076-3271"],"issn-type":[{"value":"2076-3271","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,9]]}}}