Abstract
Purpose
Salivary gland tumors are complex and have a great histomorphological diversity; more than 30 histological subtypes are currently described and the study of proteins that help understand and differentiate these tumors is essential. We aimed to analyze the immunoexpression of cyclooxygenase-2 (COX-2) and cyclin D1 proteins in pleomorphic adenomas (PA), mucoepidermoid carcinomas (MEC) and adenoid cystic carcinomas (AdCC) of salivary glands.
Methods
A total of 38 PA, 12 AdCC and 12 MEC underwent immunohistochemical study by the polymeric biotin-free technique. Immunopositive cells were analyzed semi-quantitatively. For statistical analysis, a significance level was set at p ≤ 0.05.
Results
Overall, these tumors were more prevalent in women (n = 37). The mean age of these patients was 58-year-old and the parotid gland was the most affected anatomic site (n = 33). All cases of AdCC and MEC showed immunopositivity to cyclin D1; however, 39.5% of the PAs were negative (p < 0.001). Regarding COX-2 immunoexpression, we observed that all cases of CME were positive, whereas 60.5% of the PA and 75% of the CAC analyzed were completely negative (p = 0.042).
Conclusions
The overexpression of COX-2, observed only in MEC, emphasizes that salivary gland tumors have different profiles. Cyclin D1 is more immunoexpressed in malignant tumors. Together, these immunohistochemical findings may be useful in differentiating the studied tumors.
Similar content being viewed by others
References
Seethala RR, Stenman G (2017) Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: tumors of the salivary gland. Head Neck Pathol 11(1):55–67. https://doi.org/10.1007/s12105-017-0795-0
Valstar MH, de Ridder M, van den Broek EC, Stuiver MM, van Dijk BAC, van Velthuysen MLF, Balm AJM, Smeele LE (2017) Salivary gland pleomorphic adenoma in the Netherlands: a nationwide observational study of primary tumor incidence, malignant transformation, recurrence, and risk factors for recurrence. Oral Oncol 66:93–99. https://doi.org/10.1016/j.oraloncology.2017.01.004
Andisheh-Tadbir A, Dehghani-Nazhvani A, Ashraf MJ, Khademi B, Mirhadi H, Torabi-Ardekani S (2016) MTA1 expression in benign and malignant salivary gland tumors. Iran J Otorhinolaryngol 28:51–59
Jour G, West K, Ghali V, Shank D, Ephrem G, Wenig BM (2013) Differential expression of p16(INK4A) and cyclin D1 in benign and malignant salivary gland tumors: a study of 44 Cases. Head Neck Pathol 7(3):224–231. https://doi.org/10.1007/s12105-012-0417-9
John RR, Malathi N, Ravindran C, Anandan S (2017) Mini review: multifaceted role played by cyclin D1 in tumor behavior. Indian J Dent Res 28(2):187–192. https://doi.org/10.4103/ijdr.IJDR_697_16
Liu Y, Sun H, Hu M, Zhang Y, Chen S, Tighe S, Zhu Y (2017) The role of cyclooxygenase-2 in colorectal carcinogenesis. Clin Colorectal Cancer 16(3):165–172. https://doi.org/10.1016/j.clcc.2016.09.012
Pang LY, Hurst EA, Argyle DJ (2016) Cyclooxygenase-2: a role in cancer stem cell survival and repopulation of cancer cells during therapy. Stem Cells Int 2016:2048731
Yang G, Deng Q, Fan W, Zhang Z, Xu P, Tang S, Wang P, Wang J, Yu M (2017) Cyclooxygenase-2 expression is positively associated with lymph node metastasis in nasopharyngeal carcinoma. PLoS One 12(3):e0173641. https://doi.org/10.1371/journal.pone.0173641
Xu F, Li M, Zhang C, Cui J, Liu J, Li J, Jiang H (2017) Clinicopathological and prognostic significance of COX-2 immunohistochemical expression in breast cancer: a meta-analysis. Oncotarget 8(4):6003–6012. https://doi.org/10.18632/oncotarget.13990
Liu B, Wen JK, Li BH, Fang XM, Wang JJ, Zhang YP, Shi CJ, Zhang DQ, Han M (2011) Celecoxib and acetylbritannilactone interact synergistically to suppress breast cancer cell growth via COX-2-dependent and -independent mechanisms. Cell Death Dis 2:e185. https://doi.org/10.1038/cddis.2011.64
Chae SW, Sohn JH, Kim DH, Choi YJ, Park YL, Kim K, Cho YH, Pyo JS, Kim JH (2011) Overexpressions of cyclin B1, cdc2, p16 and p53 in human breast cancer: the clinicopathologic correlations and prognostic implications. Yonsei Med J 52(3):445–453. https://doi.org/10.3349/ymj.2011.52.3.445
Lee EY, Kang JY, Kim KW (2015) Expression of cyclooxygenase-2, peroxiredoxin I, peroxiredoxin 6 and nuclear factor-κB in oral squamous cell carcinoma. Oncol Lett 10(5):3129–3136
Solomon MC, Vidyasagar MS, Fernandes D, Guddattu V, Mathew M, Shergill AK, Carnelio S, Chandrashekar C (2016) The prognostic implication of the expression of EGFR, p53, cyclin D1, Bcl-2 and p16 in primary locally advanced oral squamous cell carcinoma cases: a tissue microarray study. Med Oncol 33(12):138
Akrish S, Peled M, Ben-Izhak O, Nagler RM (2009) Malignant salivary gland tumors and cyclo-oxygenase-2: a histopathological and immunohistochemical analysis with implications on histogenesis. Oral Oncol 45(12):1044–1050. https://doi.org/10.1016/j.oraloncology.2009.07.016
Tian Z, Li L, Wang L, Hu Y, Li J (2010) Salivary gland neoplasms in oral and maxillofacial regions: a 23-year retrospective study of 6982 cases in an eastern Chinese population. Int J Oral Maxillofac Surg 39(3):235–242. https://doi.org/10.1016/j.ijom.2009.10.016
Gao M, Hao Y, Huang MX, Ma DQ, Chen Y, Luo HY, Gao Y, Cao ZQ, Peng X, Yu GY (2017) Salivary gland tumours in a northern Chinese population: a 50-year retrospective study of 7190 cases. Int J Oral Maxillofac Surg 46(3):343–349. https://doi.org/10.1016/j.ijom.2016.09.021
Bolat Kucukzeybek B, Vedat Bayoglu I, Kucukzeybek Y, Alacacioglu A, Yigit S, Akder Sari A, Akyol M, Oktay Tarhan M (2017) The prognostic significance of cyclin D1 expression in patients with triple-negative breast cancer. J BUON 22(4):947–952
Kumar B, Yadav A, Brown NV, Zhao S, Cipolla MJ, Wakely PE, Schmitt AC, Baiocchi RA, Teknos TN, Old M, Kumar P (2017) Nuclear PRMT5, cyclin D1 and IL-6 are associated with poor outcome in oropharyngeal squamous cell carcinoma patientsand is inversely associated with p16-status. Oncotarget 8(9):14847–14859. https://doi.org/10.18632/oncotarget.14682
Qu K, Wang Z, Fan H, Li J, Liu J, Li P, Liang Z, An H, Jiang Y, Lin Q, Dong X, Liu P, Liu C (2017) MCM7 promotes cancer progression through cyclin D1-dependent signaling and serves as a prognostic marker for patients with hepatocellular carcinoma. Cell Death Dis 8(2):e2603. https://doi.org/10.1038/cddis.2016.352
Jen J, Lin LL, Lo FY, Chen HT, Liao SY, Tang YA, Su WC, Salgia R, Hsu CL, Huang HC, Juan HF, Wang YC (2017) Oncoprotein ZNF322A transcriptionally deregulates alpha-adducin, cyclin D1 and p53 to promote tumor growth and metastasis in lung cancer. Oncogene 36(36):5219. https://doi.org/10.1038/onc.2017.203
Patel RS, Rose B, Bawdon H, Hong A, Lee CS, Fredericks S, Gao K, O’Brien CJ (2007) Cyclin D1 and p16 expression in pleomorphic adenoma and carcinoma ex pleomorphic adenoma of the parotid gland. Histopathology 51(5):691–696
Hugo HJ, Saunders C, Ramsay RG, Thompson EW (2015) New insights on COX-2 in chronic inflammation driving breast cancer growth and metastasis. J Mammary Gland Biol Neoplasia 20(3–4):109–119. https://doi.org/10.1007/s10911-015-9333-4
Zhou X, Shi X, Ren K, Fan GT, Wu SJ, Zhao JN (2015) Celecoxib inhibits cell growth and modulates the expression of matrix metalloproteinases in human osteosarcoma MG-63 cell line. Eur Rev Med Pharmacol Sci 19(21):4087–4097
Kuźbicki Ł, Lange D, Stanek-Widera A, Chwirot BW (2016) Intratumoral expression of cyclooxygenase-2 (COX-2) is a negative prognostic marker for patients with cutaneous melanoma. Melanoma Res 26(5):448–456. https://doi.org/10.1097/CMR.0000000000000282
Whynott RM, Manahan P, Geisler JP (2016) Vascular endothelial growth factor (VEGF) and cyclooxygenase 2 (COX 2) immunostaining in ovarian cancer. Eur J Gynaecol Oncol 37(2):164–166
Wang D, Guo XZ, Li HY, Zhao JJ, Shao XD, Wu CY (2014) Prognostic significance of cyclooxygenase-2 protein in pancreatic cancer: a meta-analysis. Tumour Biol 35(10):10301–10307. https://doi.org/10.1007/s13277-014-2260-y
Song J, Su H, Zhou YY, Guo LL (2014) Cyclooxygenase-2 expression is associated with poor overall survival of patients with gastric cancer: a meta-analysis. Dig Dis Sci 59(2):436–445. https://doi.org/10.1007/s10620-013-2917-1
Turk HM, Camci C, Sevinc A, Bukyukberber S, Sari I, Adli M (2012) Cyclooxygenase-2 expression is not a marker of poor survival in lung cancer. Asian Pac J Cancer Prev 13(1):315–318
Lee JW, Park JH, Suh JH, Nam KH, Choe JY, Jung HY, Chae JY, Moon KC (2012) Cyclooxygenase-2 expression and its prognostic significance in clear cell renal cell carcinoma. Korean J Pathol 46(3):237–245. https://doi.org/10.4132/KoreanJPathol.2012.46.3.237
Cho NP, Han HS, Soh Y, Son HJ (2007) Overexpression of cyclooxygenase-2 correlates with cytoplasmic HuR expression in salivary mucoepidermoid carcinoma but not in pleomorphic adenoma. J Oral Pathol Med 36(5):297–303
Shishodia S, Koul D, Aggarwal BB (2004) Cyclooxygenase (COX)-2 inhibitor celecoxib abrogates TNF-induced NF-kappa B activation through inhibition of activation of I kappa B alpha kinase and Akt in human non-small cell lung carcinoma: correlation with suppression of COX-2 synthesis. J Immunol 173:2011–2022
Acknowledgements
This work was supported by the Brazilian National Council for Scientific and Technological Development (CNPq) and Coordination for the Improvement of Higher Education Personnel (CAPES).
Funding
No funding was received.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
All authors declare that they have no conflicts of interest.
Research involving human participants and/or animals
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Ethical approval for this study was obtained from the relevant local ethics committees (CEP/UPE no 243/11).
Informed consent
Informed consent was obtained from all individual participants included in the study.
Rights and permissions
About this article
Cite this article
Tenório, J.d.R., da Silva, L.P., Xavier, M.G.d.A. et al. Differential expression of cyclooxygenase-2 and cyclin D1 in salivary gland tumors. Eur Arch Otorhinolaryngol 275, 2341–2347 (2018). https://doi.org/10.1007/s00405-018-5058-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00405-018-5058-5