sdj-10071

Co-expression of BubR1 and UCHL1 in salivary gland tumors

*Mohammed K. Mahmood, **Balkees T. Garib, **Marwa A. Hamied

* Said Sadiq Hospital, Sulaimani, Iraq.

** Department of Oral Diagnosis, College of Dentistry, University of Sulaimani, Sulaimani, Iraq.

Submitted: 14/03/2018; Accepted: 18/05/2018; Published 31/08/2018

DOI: https://doi.org/10.17656/sdj.10071

Abstract

Objective: Salivary gland tumors (SGTs) are one of the most heterogeneous and challenging neoplasms affects human. Several biomarkers have been used to study proliferation, angiogenesis, prognosis, metastasis and recurrence of SGTs. The aim of this study was to evaluate, compare and correlate the co-expression of Budding Uninhibited by Benz imidazole Related 1 (BubR1) and Ubiquitin C-terminal hydrolase-L1 (UCHL1) immunomarkers in SGTs.

Methods: The immunohistochemical expression of BubR1 and UCHL1 were performed with formalin fixed paraffin embedded tissue sections of 35 retrieved blokes of SGTs. The expression, pattern of reactivity, intensity and subcellular localization of these markers are studied. T-test was used to find statistical difference in expression immunomarkers.

Results: All of the cases were positive for both BubR1 and UCHL1. The intensity of reaction differed between the tumor types. A significant difference was seen in the expression of BubR1 in benign versus malignant tumors (P=.002) and pleomorphic adenoma versus mucoepidermoid carcinoma (P=.001). While statistically significant difference was not seen in the expression of UCHL1 between the tumors mentioned above (P=.81 and P=.83, respectively). Finally, there was a significant difference between the expressions of BubR1 and UCHL1 in SGTs (P=.001), indicating a higher expression of UCHL1 in SGTs.

Conclusions: UCHL1 has a higher percentage and intensity of reactivity in SGTs as compared to BubR1, While BubR1 is a better immunomarker for distinguishing between benign and malignant tumors.

Keywords: BubR1, UCHL1, Immunohistochemistry, Salivary gland tumors.

Full Article - PDF

References:

1. Speight PM and Barrett AW. Prognostic factors in malignant tumors of the salivary glands. Br J Oral Maxillofac Surg. 2009;47(8):587-93.

2. Nagao T, Sato E, Inoue R, Oshiro H, Takahashi RH, Nagai T, et al. Immunohistochemical analysis of salivary gland tumors: application for surgical pathology practice. Histochem Cytochem. 2012;45(5): 269-82.

3. Ito FA, Jorge J, Vargas PA and Lopes MA. Histopathological findings of pleomorphic adenomas of the salivary glands. Medi Oral Pathol 2009; 14: 57-61.

4. Shieh YS, Chang LC, Chiu KC, Wu CW, Lee HS. Cadherin and catenin expression in mucoepidermoid carcinoma: correlation with histopathologic grade, clinical stage, and patient outcome. J Oral Pathol Med. 2003;32(5):297-304.

5. Lee KS, Kwak Y, Nam KH, Kim D-W, Kang S-B, Choe G, et al. Favorable prognosis in colorectal cancer patients with co-expression of c-MYC and ß-catenin. BMC Cancer. 2016;16(1):730.

6. Park H-Y, Jeon Y-K, Shin H-J, Kim I-J, Kang H-C, Jeong S-J, et al. Differential promoter methylation may be a key molecular mechanism in regulating BubR1 expression in cancer cells. Exper Mol Med. 2007;39(2):195-204.

7. 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):933-38.

8. Ko YH, Roh JH, Son YI, Chung MK, Jang JY, Byun H, et al. Expression of mitotic checkpoint proteins BUB1B and MAD2L1 in salivary duct carcinomas. J Oral Pathol and Med. 2010;39(4):349-55.

9. Schröder, C, Milde-Langosch K, Gebauer F, Schmid K, Mueller V, Wirtz RM, et al. Prognostic relevance of ubiquitin C-terminal hydrolase L1 mRNA and protein expression in breast cancer patients. J Cancer Res Clin Oncol. 2013;139(10):1745-55.

10. Durret ML, Mydlarz WK, Shao C, Zahurak ML, Chuang AY, Hoque MO, et al. Quantitative methylation profiles for multiple tumor suppressor gene promoters in salivary gland tumors. PLoS One 2010; 5(5): e10828.

11. Hamied MA, Garib BT, Mohammad DN. UCHL1 expression in OSCC in relation to the invasive front grading system. IOSR-JDMS. 2015;14(7):93-97.

12. Maciejczyk A, Szelachowska J, Czapiga B, Matkowski R, Hałoń A, Györffy B, and Surowiak P. Elevated BUBR1 expression is associated with poor survival in early breast cancer patients: 15-year follow-up analysis. J Histochem and Cytochem. 2013; 61(5):330-39.

13. Burum-Auensen E, Deangelis PM, Schjølberg AR, Røislien J, Andersen SN & Clausen O. Subcellular localization of the spindle proteins Aurora A, Mad2, and BUBR1 assessed by immunohistochemistry. J Histochem & Cytochem. 2007;55(5):477-86.

14. Lee Y, Choi E, Kim MA, Park P, Park N & Lee H. BubR1 as a prognostic marker for recurrence-free survival rates in epithelial ovarian cancers. Br J Cancer. 2009;101(3):504-10.

15. Hsieh P-C, Chen Y-K, Tsai K-B, Shieh T-Y, Chang Y-Y, Chang J-G, et al. Expression of BUBR1 in human oral potentially malignant disorders and squamous cell carcinoma. J Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;109(2):257-67.

16. Lira RC, Miranda FA, Guimarães M, Simões RT, Donadi EA, Soares CP, et al. BUBR1 expression in benign oral lesions and squamous cell carcinomas: correlation with human papillomavirus. Oncol Rep 2010;23(4):1027-36.

17. Hurst-Kennedy J, ChinL-S and LiL. Ubiquitin C-terminal hydrolase l1 in tumorigenesis. Biochem Res Int. 2012;2012: 123706.

18. Xiang T, Li L, Yin X, Yuan C, Tan C, Su X, et al. The ubiquitin peptidase UCHL1 induces G0/G1 cell cycle arrest and apoptosis through stabilizing p53 and is frequently silenced in breast cancer. PloS one 2012; 7(1):e29783.

19. Lowe J, McDermott H, Landon M, Mayer RJ, and Wilkinson KD. Ubiquitin carboxyl-terminal hydrolase (PGP9.5) is selectively present in ubiquitinated inclusion bodies characteristic of human neurodegenerative diseases. J Pathol. 1990;161(2): 153-60.

20. Bheda A, Gullapalli A, Caplow M, Pagano JS & Shackelford J. Ubiquitin editing enzyme UCHL1 and microtubule dynamics: implication in mitosis. Cell Cycle. 2010;9(5):980-94.

21. Caballero OL, Resto V, Patturajan M, Meerzaman D, Guo MZ, Engles J, et al. Interaction and colocalization of PGP9. 5 with JAB1 and p27Kip1. Oncogene. 2002;21(19):3003-10.

22. Tomita T. PGP 9.5 immunocytochemical staining for pancreatic endocrine tumors. Islets. 2013;5(3):122-128.

This work is licensed under a Creative Commons Attribution 4.0 International License.