Issues‎ > ‎vol7no2‎ > ‎

sdj.10129

Immunohistochemical Expression of BubR1 and Telomerase in Minor Salivary Gland Tissue Adjacent to Oral Squamous Cell Carcinoma

 Marwa A. Hamied*
 
 *Department of Oral Diagnosis, College of Dentistry, University of Sulaimani, Sulaimani, Iraq.
 
 
Submitted: September 13, 2020, Accepted: March 11, 2021, Published: June 1, 2021.
 
DOI: https://doi.org/10.17656/sdj.10129

Abstract

ObjectivesEvaluation of the expression of tissue markers in the parenchyma within the area adjacent to a primary tumor is critical in cancer progression, prevention, and identification of early changes in the field of cancerization. The present study aimed to evaluate BubR1 and telomerase activity in minor salivary gland tissue adjacent to oral squamous cell carcinoma (OSCC) with their clinicopathological features.          

MethodsFour-micron tissue sections from 21 formalin-fixed paraffin blocks of OSCC surgical margins were prepared and stained for anti-BubR1 and anti-telomerase antigens.      

Results: The studied sample included 71.4% males and 28.6% females, and the most prevalent site was buccal mucosa (42.9%). The total sample showed a high (71.4%) BubR1 expression, while telomerase was expressed in 42.9%. BubR1 was expressed significantly in the buccal mucosa (p=0.000) in the myoepithelial (cytoplasmic) and ductal cells (cytoplasmic and mixed). In comparison, telomerase showed significant myoepithelial mixed and cytoplasmic expression of buccal mucosa (p=0.013) and nuclear expression in ductal cells within the tongue (p=0.05). Both markers showed altered expression and predominated significantly in cases adjacent to poorly differentiated OSCC (p<0.05). Lastly, a moderate/strong correlation between the aberrant accumulation of BubR1 and telomerase was found (r=0.5-0.8, p<0.05).  

ConclusionsElevated expression of BubR1 and telomerase was found in the minor salivary gland adjacent to OSCC. Therefore, they represent a valuable tool to identify molecular changes in the field of cancerization. Cases of OSCC excised from buccal mucosa and tongue required a regular follow-up, especially poorly differentiated OSCCs. The elevated expression of both markers positively regulates each other.


Keywords: BubR1, Telomerase, Minor salivary gland; OSCC.                                                                                                                                                                                                                          Full Article - PDF 

                       


References:

1.Farah CS, John K, Wu J. Contemporary assessment and management of head and neck cancer surgical margins. In: Editor Marcu LG. Contemporary issues in head and neck cancer management. InTechOpen; 2015. p. 75–130. 
2. Dou Z, Prifti DK, Gui P, Liu X, Elowe S, Yao X. Recent progress on the localization of the spindle assembly checkpoint machinery to kinetochores. Cells. 2019;8(3):1–15. 
3. Park HY, Jeon YK, Shin HJ, Kim IJ, Kang HC, Jeong SJ, et al. Differential promoter methylation may be a key molecular mechanism in regulating BubR1 expression in cancer cells. Exp Mol Med. 2007;39(2):195–204. 
4. Hsieh PC, Chen YK, Tsai KB, Shieh TY, Chang YY, Chang JG, et al. Expression of BUBR1 in human oral potentially malignant disorders and squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;109(2):257– 67. 
5. Li F, Kim H, Ji Z, Zhang T, Chen B, Ge Y, et al. The BUB3-BUB1 complex promotes telomere DNA replication. Mol Cell. 2018; 70(3):395–407. 
6. Belair CD, Yeager TR, Lopez PM RC. Telomerase activity : a biomarker of cell proliferation, not malignant transformation. Cell Biol. 1997;94(25):13677–82. 
7. Shigeishi H, Sugiyama M, Tahara H, Ono S, Bhawal UK, Okura M, et al. Increased telomerase activity and hTERT expression in human salivary gland carcinomas. Oncol Lett. 2011;2(5):845–50. 
8. Mao L, El-Naggar AK, Fan Y-H, Lee JS, Lippman SM, Kayser S, et al. Telomerase activity in head and neck squamous cell carcinoma and adjacent tissues. Cancer Res. 1996;56(24):5600 LP–5604. 
9. Kannan S, Tahara H, Yokozaki H, Mathew B, Nalinakumari KR, Nair MK, et al. Telomerase activity in premalignant and malignant lesions of human oral mucosa. Cancer Epidemiol Biomarkers Prev. 1997;6(6):413–20. 
10. Ibraheem BF, Mohammad DN, Hamied MA. Expression of β-catenin in minor salivary glands adjacent to oral squamous cell carcinoma. Sulaimani Dent. J. 2020;7(2):9-15. 
11. Mastoraki A, Ioannidis E, Apostolaki A, Patsouris E, Aroni K. PGP 9.5, and cyclin D1 coexpression in cutaneous squamous cell carcinomas. Int J Surg Pathol. 2009;17(6):413–20. 
12. Lydiatt WM, Anderson PE, Bazzana T, Casale M, Hughes CJ, Huvos AG, et al. Molecular support for field cancerization in the head and neck. Cancer. 1998;82(7):1376–80. 
13. Sathiasekar AC, Mathew DG, Jaish Lal MS, Arul Prakash AA, Goma Kumar KU. Oral field cancerization and its clinical implications in the management in potentially malignant disorders. J Pharm Bioallied Sci. 2017;9(Suppl 1):S23–5. 
14. Hamied MA. β-catenin expression in perilesional area of different grades of oral squamous cell carcinoma. Sulaimani Dent. J. 2016;3(1):25-9. 
15. Mohammad DN. Perilesional sites of OSCC had altered P-cadherin expression. Sulaimani Dent J. 2016;3(2):78-83. 
16. Rizzardi C, Torelli L, Barresi E, Schneider M, Canzonieri V, Biasotto M, et al. BUBR1 expression in oral squamous cell carcinoma and its relationship to tumor stage and survival. Head Neck. 2011;33(5):727–33. 
17. Mohammed IJ. Expression of ubiquitin C-terminal hydrolase-L1 in minor normal salivary gland tissues in perilesional area to OSCC. Tikrit J Dent Sci. 2018;6(1):12–8. 
18. Hu MIN, Liu Q, Song P, Zhan X, Luo MIN, Liu C, et al. Abnormal expression of the mitotic checkpoint protein BubR1 contributes to the anti- microtubule drug resistance of esophageal squamous cell carcinoma cells. Oncol Reports. 2013;29(1):185–92. 
19. Sravya T, Sivaranjani Y, Rao GV. Immunohistochemical expression of budding uninhibited by benzimidazole related 1 in leukoplakia and oral squamous cell carcinoma. J Oral Maxillofac Pathol. 2016;20(1):71–7. 
20. Burum-Auensen E, De Angelis PM, Schjølberg AR, Kravik KL, Aure M, Clausen OP. Subcellular localization of the spindle proteins Aurora A, Mad2, and BUBR1 assessed by immunohistochemistry. J Histochem Cytochem 2007;55(5):477-86. 
21. Lira RC, Miranda FA, Guimarães MC, Simões RT, Donadi EA SC, et al. BUBR1 expression in benign oral lesions and squamous cell carcinomas: correlation with human papillomavirus. Oncol Rep. 2010;23(4):1027-36. 
22. Mahmood MK, Garib BT, Hamied MA. Co- expression of BubR1 and UCHL1 in salivary gland tumors. Sulaimani Dent J. 2018;5(1):1–15. 
23. Shigeishi H, Yoneda S, Taki M, Nobumori T, Ohta K, Higashikawa K, et al. Correlation of human Bub1 expression with tumor-proliferating activity in salivary gland tumors. Oncol Rep. 2006;15(4):933–8. 
24. Patel MM, Parekh LJ, Jha FP, Sainger RN, Patel JB, Patel DD, et al. Clinical usefulness of telomerase activation and telomere length in head and neck cancer. Head Neck. 2002;24(12):1060–7. 
25. Raghunandan BN, Sanjai K, Kumaraswamy J, Papaiah L, Pandey B, Jyothi BM. Expression of human telomerase reverse transcriptase protein in oral epithelial dysplasia and oral squamous cell carcinoma: an immunohistochemical study. J Oral Maxillofac Pathol. 2016;20(1):96–101.
26. Ries JC, Hassfurther E, Steininger H, Kloss FR, Wiltfang J, Girod SC, et al. Correlation of telomerase activity, clinical prognosis and therapy in oral carcinogenesis. Anticancer Res. 2001;21(2A):1057–63. 
27. Curran AJ, St Denis K, Irish J, Gullane PJ, MacMillan C, Kamel-Reid S. Telomerase activity in oral squamous cell carcinoma. Arch Otolaryngol Head Neck Surg. 1998;124(7):784–8. 
28. Patel MM, Patel DD, Parekh LJ, Raval GN, Rawal RM. Evaluation of telomerase activation in head and neck cancer. Oral Oncol. 1999;35(5):510–15. 
29. Liao J, Mitsuyasu T, Yamane K, Ohishi M. Telomerase activity in oral and maxillofacial tumors. Oral Oncol. 2000;36(4):347–52. 
30. Fabricius E, Gurr U, Wildner G. Telomerase activity levels in the surgical margin and tumour distant tissue of the squamous cell carcinoma of the head-and-neck. Anal Cell Pathol. 2002;24(1):25– 39. 
31. Abdulrahman SS, Mohammad DN, Hamied MA, Abdulqadir MO. Immunohistochemical evaluation of salivary gland tumors differentiation and proliferation by using calponin and telomerase. Saudi Dent J. 2019;31(1):105-14. 
32. Chen L, Huang J, Li Z. Detection of telomerase activity in salivary tumor and its significance. Hunan yi ke da xue xue bao. 2002;27(3):282–4. 
33. Garib BT, Mohammad DN, Hamied MA. Immunohistochemical expression of bubr1 and telomerase in oral squamous cell carcinoma. Sulaimani Dent J. 2020;7(1):73–9. 
34. Sumida T, Sogawa K, Hamakawa H, Sugita A, Tanioka H, Ueda N. Detection of telomerase activity in oral lesions. J Oral Pathol Med. 1998;27:111–15. 
35. Rai A, Naikmasur VG, Sattur A. Quantification of telomerase activity in normal oral mucosal tissue and oral squamous cell carcinoma. Indian J Med Paediatr Oncol. 2016;37(3):183–8. 
36. Miyazaki Y, Yoshida N, Nozaki T, Inoue H, Kikuchi K, Kusama K. Telomerase activity in the occurrence and progression of oral squamous cell carcinoma. J Oral Sci. 2015;57(4):295–303. 
37. Chang LY, Lin SC, Chang CS, Wong YK, Hu YC, Chang KW. Telomerase activity and in situ telomerase RNA expression in oral carcinogenesess. J Oral Pathol Med. 1999;28(9):389–96. 
38. Rajendran R, Sunil, Twinkle SP, Anikumar T V, Annie J. Cell death does not herald epithelial involution ("atrophy") in oral submucous fibrosis: a TEM study. Indian J Dent Res. 2004;15(1):13–9.
 
 
 
 
 
 






 
Creative Commons License © The Authors, published by University of Sulaimani, College of Dentistry