Objective
This study aimed to compare the immunoexpression profile of tumor stem cell (TSC)
biomarkers CD44, aldehyde dehydrogenase 1 (ALDH1), OCT4, and SOX2 in salivary gland
tumors (SGTs).
Study Design
Sixty tissue specimens of SGTs, including 20 pleomorphic adenomas, 20 adenoid cystic
carcinomas (ACCs), and 20 mucoepidermoid carcinomas, in addition to 4 samples of normal
glandular tissue, were subjected to immunohistochemistry. The expression of the biomarkers
in the parenchyma and stroma was evaluated. Data were analyzed statistically by nonparametric
tests (P < .05).
Results
Higher parenchymal expression of ALDH1, OCT4, and SOX2 was observed in pleomorphic
adenomas, ACCs, and mucoepidermoid carcinomas, respectively. Most ACCs did not express
ALDH1. Higher immunoexpression of ALDH1 in major SGTs (P = .021) and of OCT4 in minor SGTs (P = .011) was found. Immunoexpression of SOX2 was related to lesions without myoepithelial
differentiation (P < .001) and malignant behavior (P = .002). Furthermore, OCT4 was related to myoepithelial differentiation (P = .009). CD44 expression was related to a better prognosis. Stromal immunoexpressions
of CD44, ALDH1, and OCT4 were higher in malignant SGTs.
Conclusions
Our findings suggest the participation of TSCs in the pathogenesis of SGTs. We emphasize
the need for further investigations into the presence and role of TSCs in the stroma
of these lesions.
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References
- Salivary gland cancer stem cells.Oral Oncol. 2013; 49: 845-853
- Histogenesis of salivary gland neoplasms.Indian J Cancer. 2013; 50: 361
- Characteristics of salivary gland tumours in the United Arab Emirates.Ecancermedicalscience. 2015; 9: 583
- Salivary gland tumors.Ann Plast Surg. 2020; 84: S26-S33
- World Health Organization Classification of Tumours.4th ed. International Agency for Research on Cancer, Lyon, France2017
- Salivary gland tumors: a diagnostic dilemma!.J Maxillofac Oral Surg. 2015; 14: 438-442
- Histopathology of the Salivary Glands.Springer, Heidelberg, Germany2014
- Pleomorphic adenoma: a systematic review.Int J Clin Pediatr Dent. 2020; 13: 285-287
- Immunology of cancer stem cells in solid tumours. A review.Eur J Cancer. 2014; 50: 649-655
- Expression of stem cell marker CD44 in selected benign and malignant salivary gland tumors.Saudi J Oral Sci. 2018; 5: 80
- Cancer stem cell markers in head and neck squamous cell carcinoma.Stem Cells Int. 2013; : 1-13
- HPV infection of the head and neck region and its stem cells.J Dent Res. 2015; 94: 1532-1543
- Embryonic stem cells markers Oct4 and Nanog correlate with perineural invasion in human salivary gland mucoepidermoid carcinoma.J Oral Pathol Med. 2017; 46: 112-120
- CD44 expression in pleomorphic adenoma, carcinoma ex pleomorphic adenoma and their adjacent normal salivary glands.Dent Res J (Isfahan). 2018; 15: 361-366
- A pathological classification of pleomorphic adenoma of the salivary glands.HNO. 1976; 24: 415-426
- Adenoid cystic carcinoma.in: WHO Classification of Head and Neck Tumors. 4th ed. International Agency for Research on Cancer, Lyon, France2017: 221-222
- Mucoepidermoid carcinoma: a clinicopathologic study of 80 patients with special reference to histologic grading.Am J Surg Pathol. 2001; 25: 835-845
- CD44 variant isoforms in head and neck squamous cell carcinoma progression.Laryngoscope. 2009; 119: 1518-1530
- Correlation of ALDH1, CD44, OCT4 and SOX2 in tongue squamous cell carcinoma and their association with disease progression and prognosis.J Oral Pathol Med. 2014; 43: 492-498
- Increased expression of ALDH-1 is associated with clinical parameters of salivary glands neoplasms.Exp Mol Pathol. 2020; 117104552
- Taxonomy of salivary gland neoplasm.J Clin Diagn Res. 2014; 8: 291-293
- Cancer stem cells in head and neck squamous cell carcinoma: identification, characterization and clinical implications.Cancers (Basel). 2019; 11: 616
- Association of SOX2, OCT4 and WNT5A expression in oral epithelial dysplasia and oral squamous cell carcinoma: an immunohistochemical study.Head Neck Pathol. 2020; 14: 749-757
- CD24 and CD44 in salivary gland pleomorphic adenoma and in human salivary gland morphogenesis: differential markers of glandular structure or stem cell indicators?.Histopathology. 2013; 62: 1075-1082
- ALDH1 immunohistochemical expression and its significance in salivary adenoid cystic carcinoma.Head Neck. 2013; 35: 575-578
- High expression of SOX2 is associated with poor prognosis in patients with salivary gland adenoid cystic carcinoma.Int J Mol Sci. 2014; 15: 8393-8406
- Expression of cell adhesion molecule CD44 in mucoepidermoid carcinoma and its association with the tumor behavior.Head Face Med. 2016; 12: 1-5
- Immunohistochemical expression of CD56 and ALDH1 in common salivary gland tumors.Iran J Otorhinolaryngol. 2016; 28: 389-397
- Increased SOX2 expression in salivary gland carcinoma ex pleomorphic adenoma progression: an association with adverse outcome.Virchows Arch. 2017; 471: 775-784
- Cancer stem cell markers in adenocarcinoma of the salivary glands - reliable prognostic markers?.Eur Arch Otorhinolaryngol. 2021; 278: 2517-2528
- Immunohistochemical expression of OCT4 and CD44 in major and minor salivary gland neoplasms.Braz Oral Res. 2021; 35: e073
- ALDH/CD44 identifies uniquely tumorigenic cancer stem cells in salivary gland mucoepidermoid carcinomas.Oncotarget. 2015; 6: 26633-26650
- Role of CD44 in tumor-initiating cells of salivary gland pleomorphic adenoma: more than a surface biomarker.Oral Dis. 2020; 26: 547-557
- Expression and localization of osteopontin, homing cell adhesion molecule/CD44, and integrin αvβ3 in pleomorphic adenoma, polymorphous low-grade adenocarcinoma, and adenoid cystic carcinoma.Oral Surg Oral Med Oral Pathol Oral Radiol. 2013; 116: 743-751
- Expression and localization of osteopontin, homing cell adhesion molecule/CD44, and integrin αvβ3 in mucoepidermoid carcinoma and acinic cell adenocarcinoma of salivary gland origin.Oral Surg Oral Med Oral Pathol Oral Radiol. 2014; 118: 320-329
- CD44/CD24 immunophenotypes on clinicopathologic features of salivary glands malignant neoplasms.Diagn Pathol. 2013; 8: 1-11
- Expression of CD44, CD44v9, ABCG2, CD24, Bmi‑1 and ALDH1 in stage I and II oral squamous cell carcinoma and their association with clinicopathological factors.Oncol Lett. 2018; 16: 1133-1140
- Cancer stem cells in oral cavity squamous cell carcinoma: a review.Front Oncol. 2017; 7: 1-10
- The identification of three cancer stem cell subpopulations within moderately differentiated lip squamous cell carcinoma.Front Surg. 2017; 4: 1-8
- The current markers of cancer stem cell in oral cancers.Life Sci. 2020; 249117483
- MyD88 is an essential component of retinoic acid–induced differentiation in human pluripotent embryonal carcinoma cells.Cell Death Differ. 2017; 24: 1975-1986
- Expression of p63 and CD44 in oral squamous cell carcinoma and correlation with clinicopathological parameters.Arch Oral Biol. 2017; 82: 160-165
- Immunohistochemical expression of CD44 in oral squamous cell carcinoma in relation to histomorphological parameters and clinicopathological factors.Histopathology. 2018; 73: 559-572
- Crosstalk between Raf-MEK-ERK and PI3K-Akt-GSK3β signaling networks promotes chemoresistance, invasion/migration and stemness via expression of CD44 variants (v4 and v6) in oral cancer.Oral Oncol. 2018; 86: 234-243
- Overexpression of cysteine-glutamate transporter and CD44 for prediction of recurrence and survival in patients with oral cavity squamous cell carcinoma.Head Neck. 2018; 40: 2340-2346
- Preoperative assessment of CD44-mediated depth of invasion as predictor of occult metastases in early oral squamous cell carcinoma.Head Neck. 2019; 41: 950-958
- Hyaluronan and CD44 expression in minor salivary gland tumors.Oral Dis. 2008; 4: 241-247
- Serum soluble CD44v6 levels in patients with oral and maxillofacial malignancy.Oral Dis. 2009; 15: 570-572
- Reduced expression of CD44 variant 9 is related to lymph node metastasis and poor survival in squamous cell carcinoma of tongue.Oral Oncol. 2000; 36: 545-549
- CD44 expression and its relationship with MMP-9, clinicopathological factors and survival in oral squamous cell carcinoma.Oral Oncol. 2007; 43: 51-59
- The molecular markers of cancer stem cells in head and neck tumors.J Cell Physiol. 2020; 235: 65-73
- Analysis of the relationship between the expression of markers of tumor stem cells (ALDH-1 and SOX-2) and the clinicopathological characteristics of salivary gland neoplasms [thesis]. Oral Pathology Postgraduate Program.Federal University of Rio Grande do Norte, 2019
- Inhibition of uPAR-TGFβ crosstalk blocks MSC-dependent EMT in melanoma cells.J Mol Med (Berl). 2015; 93: 783-794
- Lung-resident mesenchymal stem cell fates within lung cancer.Cancers (Basel). 2021; 13: 4637
- Mesenchymal stem cells induce epithelial mesenchymal transition in melanoma by paracrine secretion of transforming growth factor-β.Melanoma Res. 2017; 27: 74-84
- Suppression of PTBP1 signaling is responsible for mesenchymal stem cell induced invasion of low malignancy cancer cells.Biochim Biophys Acta Mol Cell Res. 2018; 1865: 1552-1565
- The expression profile of Oct4 and Sox2 in the carcinogenesis of oral mucosa.Int J Clin Exp Pathol. 2014; 7: 28-37
Article info
Publication history
Published online: September 29, 2022
Accepted:
September 22,
2022
Received in revised form:
September 9,
2022
Received:
March 5,
2022
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.