Immunohistochemical Study of Cancer Stem Cell marker, Tight Junction Protein, and Lymphatic Density in Malignant Salivary Gland Tumors

Authors

  • Marwa Maghrabi Department of Oral Pathology, Faculty of Dentistry, University of Tripoli, Tripoli, Libya
  • Doaa A. Farag Department of Oral and Maxillofacial Pathology, Faculty of Oral and Dental Medicine, Mansoura University, Mansoura, Egypt
  • Marwa Shakweer Department of Pathology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
  • Mohamed Negm Department of Pathology, Faculty of Medicine, Cairo University, Giza, Egypt https://orcid.org/0000-0002-6889-8086
  • Nadia A. El-Sissy Department of Oral and Maxillofacial Pathology, Faculty of Oral and Dental Medicine, Mansoura University, Mansoura, Egypt

DOI:

https://doi.org/10.3889/oamjms.2022.9305

Keywords:

Malignant salivary gland tumors, c-kit (CD117), Claudin-1, Podoplanin

Abstract

Background: CD117/c-kit, is a powerful stem cell marker for malignant salivary gland tumors in which dysregulation of c-kit is closely associated with impairment of cell adhesion molecules and cancer metastasis.

Objective: The main purpose of this work is to evaluate the immunohistochemical expression of c-kit, and claudin-1 and measure the density of lymph vessels (LVD) in common malignant salivary gland tumors by using podoplanin (D2-40) antibody.

Materials and Methods: Immunohistochemical staining with streptavidin peroxidase was used to analysis the expression of c-kit, claudin-1 and stained podoplanin (D2-40) lymphatic vessels on fifty archival paraffin blocks of malignant salivary gland tumor (MSGTs) cases included 20 cases of AdCC, 11 cases of MEC, 10 cases of CXPA,              6 cases of AcCC, and 3 cases of PAC.

Results: The immunopositivity of c-kit (CD117) was detected in 44/50 (88%) of studied cases, whereas, claudin-1 protein was observed in 35 (70%) of our specimens of MSGTs.  Count down of stained lymph vessels between examined cases was, MEC on the top, followed by CXPA, AdCC, PAC and AcCC. A direct correlation was observed between c-kit and lymphatic density, on the other hand, the inverse correlation was found d between c-kit and cld-1, as well as, between cld-1 and lymphatic density

Conclusion: Up regulation of cancer stem cell marker c-kit (CD117) expression is associated with decrease of tight junction protein cld-1 and increase the density of stained lymphatic vessels by podoplanin (D2-40) antibody which confirms the using of c-kit inhibitor to improve treatment strategy of malignant salivary gland tumors.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Carlson ER, Schlieve T. Salivary Gland Malignancies. Oral Maxillofac Surg Clin North Am. 2019;31(1):125-44. https://doi.org/10.1016/j.coms.2018.08.007 PMid:30449524 DOI: https://doi.org/10.1016/j.coms.2018.08.007

Weissman IL. Stem cells: Units of development, units of regeneration, and units in evolution. Cell. 2000;100(1):157-68. https://doi.org/10.1016/s0092-8674(00)81692-x PMid:10647940 DOI: https://doi.org/10.1016/S0092-8674(00)81692-X

Burkert NA, Wright M, Alison R. Stem cells and cancer: An intimate relationship. J Pathol. 2006;209(3):287-97. https://doi.org/10.1002/path.2016 PMid:16770755 DOI: https://doi.org/10.1002/path.2016

Liang J, Wu YL, Chen BJ, Zhang W, Tanaka Y, Sugiyama H. The C-kit receptor-mediated signal transduction and tumor-related diseases. Int J Biol Sci. 2013;9(5):435-43. https://doi.org/10.7150/ijbs.6087 PMid:23678293 DOI: https://doi.org/10.7150/ijbs.6087

Stankov K, Popovic S, Mikov M. C-KIT signaling in cancer treatment. Curr Pharm Des. 2014;20(17):2849-80. https://doi.org/10.2174/13816128113199990593 PMid:23944364 DOI: https://doi.org/10.2174/13816128113199990593

Bhat AA, Syed N, Therachiyil L, Nisar S, Hashem S, Macha MA, et al. Claudin-1, a double-edged sword in cancer. Int J Mol Sci. 2020;21(2):569. https://doi.org/10.3390/ijms21020569 PMid:31952355 DOI: https://doi.org/10.3390/ijms21020569

Tsuruo T, Fujita N. Platelet aggregation in the formation of tumor metastasis. Proc Jpn Acad Ser B Phys Biol Sci. 2008;84(6):189-98. https://doi.org/10.2183/pjab.84.189 PMid:18941298 DOI: https://doi.org/10.2183/pjab.84.189

Ran S, Volk L, Hall K, Flister MJ. Lymphangiogenesis and lymphatic metastasis in breast cancer. Pathophysiology. 2010;17(4):229-51. https://doi.org/10.1016/j.pathophys.2009.11.003 Mid:20036110 DOI: https://doi.org/10.1016/j.pathophys.2009.11.003

Wicki A, Christofori G. The potential role of podoplanin in tumour invasion. Br J Cancer. 2007;96:1-5. https://doi.org/10.1038/sj.bjc.6603518 DOI: https://doi.org/10.1038/sj.bjc.6603518

Goode RK, Auclair PL, Ellis GL. Mucoepidermoid carcinoma of the major salivary glands: Clinical and histopathologic analysis of 234 cases with evaluation of grading criteria. Cancer 1998;82(1):1217-24. https://doi.org/10.1002/(sici)1097-0142(19980401)82:7<1217:aid-cncr2>3.0.co;2-c PMid:17179989 DOI: https://doi.org/10.1002/(SICI)1097-0142(19980401)82:7<1217::AID-CNCR2>3.0.CO;2-C

Szanto PA, Luna MA, Tortoledo ME, White RA. Histologic grading of adenoid cystic carcinoma of the salivary glands. Cancer. 1984;54(6):1062-9. https://doi.org/10.1002/1097-0142(19840915)54:6<1062:aid-cncr2820540622>3.0.co;2-e PMid:6088017 DOI: https://doi.org/10.1002/1097-0142(19840915)54:6<1062::AID-CNCR2820540622>3.0.CO;2-E

Fan H, Yuan Y, Wang J, Zhou F, Zhang M, Giercksky KE, et al. CD117 expression in operable oesophageal squamous cell carcinomas predicts worse clinical outcome. Histopathology. 2013;62:1028-37. https://doi.org/10.1111/his.12111 PMid:23570416 DOI: https://doi.org/10.1111/his.12111

Lu S, Singh K, Mangray S. Claudin expression in high-grade invasive ductal carcinoma of the breast: Correlation with the molecular subtype. Mod Pathol. 2013;26(4):485-95. https://doi.org/10.1038/modpathol.2012.187 Mid:23222490 DOI: https://doi.org/10.1038/modpathol.2012.187

Parhar S, Kaur H, Vashist A, Verma S. Role of podoplanin in potentially malignant disorders and oral squamous cell carcinoma and its correlation with lymphangiogenesis. Indian J Cancer. 2015;52(4):617-22. https://doi.org/10.4103/0019-509x.178427 PMid:26960495 DOI: https://doi.org/10.4103/0019-509X.178427

Foster BM, Zaidi D, Young TR, Mobley ME, Kerr BA. CD117/c-kit in cancer stem cell-mediated progression and therapeutic resistance. Biomedicines. 2018;6(1):31. https://doi.org/10.3390/biomedicines6010031 PMid:29518044 DOI: https://doi.org/10.3390/biomedicines6010031

Pang MF, Georgoudaki AM, Lambut L, Johansson J, Tabor V, Hagikura K, et al. TGF-beta1-induced EMT promotes targeted migration of breast cancer cells through the lymphatic system by the activation of CCR7/CCL21-mediated chemotaxis. Oncogene. 2016;35(6):748-60. https://doi.org/10.1038/onc.2015.133 PMid:25961925 DOI: https://doi.org/10.1038/onc.2015.133

Uraizee I, Cipriani NA, Ginat DT. Adenoid cystic carcinoma of the oral cavity: Radiology-pathology correlation. Head Neck Pathol. 2018;12(4):562-6. https://doi.org/10.1007/s12105-017-0849-3 PMid:28879643 DOI: https://doi.org/10.1007/s12105-017-0849-3

Salehinejad J, Mohtasham N, Bagherpour A, Abbaszadeh-bidokhty H, Ghazi A. Evaluation of c-kit protein (CD117) expression in common salivary gland neoplasms. J Oral Maxillofac Pathol. 2014;18:177-82. https://doi.org/10.4103/0973-029x.140732 PMid:25328295 DOI: https://doi.org/10.4103/0973-029X.140732

Tariq H, Anjum S, Din HU, Akhtar F. Diagnostic utility of C-kit protein (CD117) expression in differentiating adenoid cystic carcinoma and polymorphous low grade Adenocarcinoma. Pak J Med Sci. 2017;33(6):1376-80. https://doi.org/10.12669/pjms.336.13373 PMid:29492062 DOI: https://doi.org/10.12669/pjms.336.13373

Aoyama T, Takasawa A, Murata M. Immunoreactivity patterns of tight junction proteins are useful for differential diagnosis of human salivary gland tumors. Med Mol Morphol. 2019;52(1):23-35. https://doi.org/10.1007/s00795-018-0199-6 PMid:29955965 DOI: https://doi.org/10.1007/s00795-018-0199-6

Lee JW, Hsiao WT, Chen HY, Hsu LP, Chen PR, Lin MD, et al. Upregulated claudin-1 expression confers resistance to cell death of nasopharyngeal carcinoma cells. Int J Cancer. 2010;126(6):1353-66. https://doi.org/10.1002/ijc.24857 PMid:19739116 DOI: https://doi.org/10.1002/ijc.24857

Upadhaya P, Barhoi D, Giri A, Bhattacharjee A, Giri S. Joint detection of claudin-1 and junctional adhesion molecule-A as a therapeutic target in oral epithelial dysplasia and oral squamous cell carcinoma. J Cell Biochem. 2019;120(10):18117-27. https://doi.org/10.1002/jcb.29115 PMid:31161679 DOI: https://doi.org/10.1002/jcb.29115

Soares AB, Martinez EF, Ribeiro PF, Barreto IS, Aguiar MC, Furuse C, et al. Factors that may influence polymorphous low-grade adenocarcinoma growth. Virchows Arch. 2017;470(4):437-43. https://doi.org/10.1007/s00428-017-2085-3 PMid:28188441 DOI: https://doi.org/10.1007/s00428-017-2085-3

Kim J, Choi S, Kim JO, Kim KK. Autophagy-mediated upregulation of cytoplasmic claudin 1 stimulates the degradation of SQSTM1/p62 under starvation. Biochem Biophys Res Commun. 2018;496(1):159-66. https://doi.org/10.1016/j.bbrc.2018.01.017 PMid:29307823 DOI: https://doi.org/10.1016/j.bbrc.2018.01.017

Jardim JF, Galvis MM, Fabelo IR, Soares FA, Lopes Pinto CA, Kowalski LP. Intratumoral lymphatic vascular density is an independent factor for disease-free and overall survival in advanced stage oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol. 2021;5(132):580-8. https://doi.org/10.1016/j.oooo.2021.07.014 PMid:34509400 DOI: https://doi.org/10.1016/j.oooo.2021.07.014

Downloads

Published

2022-04-20

How to Cite

1.
Maghrabi M, Farag DA, Shakweer M, Negm M, El-Sissy NA. Immunohistochemical Study of Cancer Stem Cell marker, Tight Junction Protein, and Lymphatic Density in Malignant Salivary Gland Tumors. Open Access Maced J Med Sci [Internet]. 2022 Apr. 20 [cited 2024 Nov. 21];10(A):879-86. Available from: https://oamjms.eu/index.php/mjms/article/view/9305