MTA1 Expression in Benign and Malignant Salivary gland Tumors

Document Type : Original


1 Prevention of Oral and Dental Disease Research Center, Department of Oral and Maxillofacial Pathology, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran.

2 Department of Oral and Maxillofacial Pathology, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran.

3 Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

4 Department of Otorhinolaryngology, Khalili Hospital, Shiraz Institute for Cancer Research, Shiraz University of Medical Sciences, Shiraz, Iran.

5 Department of Endodontics, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran.


Salivary gland tumors (SGTs) are important parts of human neoplasms. The most common SGT is pleomorphic adenoma and the most common malignant SGTs are mucoepidermoid carcinoma and adenoid cystic carcinoma (ACC). Metastasis-associated genes 1 (MTA1), a member of the nucleosome remodeling and histone deacetylation complex, is one newly discovered gene which recruits histone deacetylation, causing ATP-dependent chromosome remodeling, and regulating transcription. MTA1 had been shown to be overexpressed in malignant tumors with the enhancement of invasion and metastasis.
Materials and Methods:
Fifty-six samples of salivary tumors from the Khalili Hospital archive, including 20 cases of pleomorphic adenoma, 17 cases of mucoepidermoid carcinoma, 19 cases of ACC, and 23 cases of normal salivary gland tissues were chosen for immunohistochemical analysis of MTA1.
MTA1 expression in the malignant tumors was significantly higher than that in pleomorphic adenoma (P<0.001), and higher in pleomorphic adenoma than the normal salivary glands
(P< 0.001). In total, 69.6% of normal salivary gland tissues showed MTA1, but all cases of salivary gland tumors were positive for MTA1. High nuclear expression of MTA1 was detected in 83.3% (30/36) of the malignant salivary gland tumors and 45% (9/20) of pleomorphic adenoma, while low MTA1 expression was seen in all of the normal salivary gland tissues. No statistically significant correlation was found between MTA1 protein expression and any clinicopathological features (P>0.05).
Our findings demonstrate that MTA1 was significantly overexpressed in malignant salivary gland neoplasm in comparison to a lower level in benign pleomorphic adenoma, suggesting that MTA1 protein might be involved in carcinogenesis.


Main Subjects

1. Alves FA, Pires FR, De Almeida OP, Lopes MA, Kowalski LP. PCNA, Ki-67 and p53 expressions in submandibular salivary gland tumours. International journal of oral and maxillofacial surgery 2004; 33(6):593-7.
2. Jones AV, Franklin CD. An analysis of oral and maxillofacial pathology found in adults over a 30-year period. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 2006;35(7):392-401.
3. Speight PM, Barrett AW. Salivary gland tumours. Oral diseases. 2002;8(5):229-40. Epub 2002/10/05.
4. Ota T, Ota K, Jono H, Fujimori H, Ueda M, Shinriki S, et al. Midkine expression in malignant salivary gland tumors and its role in tumor angiogenesis. Oral oncology 2010;46(9):657-61.
5. Andisheh-Tadbir A, Ashraf MJ, Khademi B, Ahmadi Sh. Clinical implication of CD166 expression in salivary gland tumor.Tumor Biology 2015; 36(4): 2793-9.
6. Toh Y, Pencil SD, Nicolson GL. A novel candidate metastasis-associated gene, mta1, differentially expressed in highly metastatic mammary adenocarcinoma cell lines. cDNA cloning, expression, and protein analyses. The Journal of biological chemistry 1994;269(37):22958-63.
7. Toh Y, Nicolson GL. The role of the MTA family and their encoded proteins in human cancers: molecular functions and clinical implications. Clinical & experimental metastasis 2009;26(3):215-27.
8. Bowen NJ, Fujita N, Kajita M, Wade PA. Mi-2/NuRD: multiple complexes for many purposes. Biochimica et biophysica acta. 2004;1677(1-3):52-7.
9. Nicolson GL, Nawa A, Toh Y, Taniguchi S, Nishimori K, Moustafa A. Tumor metastasis-associated human MTA1 gene and its MTA1 protein product: role in epithelial cancer cell invasion, proliferation and nuclear regulation. Clinical & experimental metastasis 2003;20(1):19-24.
10. Ryu SH, Chung YH, Lee H, Kim JA, Shin HD, Min HJ, et al. Metastatic tumor antigen 1 is closely associated with frequent postoperative recurrence and poor survival in patients with hepatocellular carcinoma. Hepatology (Baltimore, Md) 2008; 47(3): 929-36.
11. Patel SG, Shah JP. TNM staging of cancers of the head and neck: striving for uniformity among diversity. CA: a cancer journal for clinicians 2005;55(4):242-58.
12. Seethala RR. An update on grading of salivary gland carcinomas. Head and neck pathology 2009; 3(1):69-77.
13. Prisco MG, Zannoni GF, De Stefano I, Vellone VG, Tortorella L, Fagotti A, et al. Prognostic role of metastasis tumor antigen 1 in patients with ovarian cancer: a clinical study. Human pathology 2012; 43(2): 282-8.
14. Eveson JW, Cawson RA. Tumours of the minor (oropharyngeal) salivary glands: a demographic study of 336 cases. Journal of oral pathology 1985;14(6): 500-9.
15. Eveson JW. Troublesome tumours 2: borderline tumours of salivary glands. Journal of clinical pathology 1992;45(5):369-77.
16. Luukkaa H, Klemi P, Hirsimaki P, Vahlberg T, Kivisaari A, Kahari VM, et al. Matrix metalloproteinase (MMP)-1, -9 and -13 as prognostic factors in salivary gland cancer. Acta oto-laryngologica  2008;128(4):482-90.
17. Manavathi B, Singh K, Kumar R. MTA family of coregulators in nuclear receptor biology and pathology. Nuclear receptor signaling 2007;5:e010.
18. Toh Y, Ohga T, Endo K, Adachi E, Kusumoto H, Haraguchi M, et al. Expression of the metastasis-associated MTA1 protein and its relationship to deacetylation of the histone H4 in esophageal squamous cell carcinomas. International journal of cancer Journal international du cancer 2004;110(3): 362-7.
19. Geng L, Deepak PA, Aija L, Fuming C, Amanda M, Robert CR, et al. Identification of Metastasis Associated Antigen 1 (MTA1) by Serological Screening of Prostate Cancer cDNA Libraries. The open biochemistry journal 2008;2:100-7.
20. Moon HE, Cheon H, Lee MS. Metastasis-associated protein 1 inhibits p53-induced apoptosis. Oncology reports. 2007;18(5):1311-4.
21. Yoo YG, Kong G, Lee MO. Metastasis-associated protein 1 enhances stability of hypoxia-inducible factor-1alpha protein by recruiting histone deacetylase 1. The EMBO journal 2006;25(6):1231-41.
22. Moon HE, Cheon H, Chun KH, Lee SK, Kim YS, Jung BK, et al. Metastasis-associated protein 1 enhances angiogenesis by stabilization of HIF-1alpha. Oncology reports 2006;16(4):929-35.
23. Achen MG, Stacker SA. Molecular control of lymphatic metastasis. Annals of the New York Academy of Sciences 2008;1131:225-34.
24. Royston D, Jackson DG. Mechanisms of lymphatic metastasis in human colorectal adenocarcinoma. The Journal of pathology 2009; 217(5):608-19.
25. Thiery JP. Epithelial-mesenchymal transitions in tumour progression. Nature reviews Cancer 2002; 2(6):442-54.
26. Kawasaki G, Yanamoto S, Yoshitomi I, Yamada S, Mizuno A. Overexpression of metastasis-associated MTA1 in oral squamous cell carcinomas: correlation with metastasis and invasion. International journal of oral and maxillofacial surgery 2008; 37(11):1039-46.
27. Xu L, Mao XY, Fan CF, Zheng HC. MTA1 expression correlates significantly with cigarette smoke in non-small cell lung cancer. Virchows Archiv : an international journal of pathology 2011;459(4):415-22.
28. Li SH, Wang Z, Liu XY. Metastasis-associated protein 1 (MTA1) overexpression is closely associated with shorter disease-free interval after complete resection of histologically node-negative esophageal cancer. World journal of surgery 2009;33(9):1876-81.
29. Moon WS, Chang K, Tarnawski AS. Overexpression of metastatic tumor antigen 1 in hepatocellular carcinoma: Relationship to vascular
invasion and estrogen receptor-alpha. Human pathology 2004;35(4):424-9.
30. Balasenthil S, Broaddus RR, Kumar R. Expression of metastasis-associated protein 1 (MTA1) in benign endometrium and endometrial adenocarcinomas. Human pathology 2006;37(6): 656-61.
31. Manavathi B, Kumar R. Metastasis tumor antigens, an emerging family of multifaceted master coregulators. The Journal of biological chemistry 2007;282(3):1529-33.
32. Andishehtadbir A, Najvani AD, Pardis S, Ashkavandi ZJ, Ashraf MJ, Khademi B, et al. Metastasis-Associated Protein 1 Expression in Oral Squamous Cell Carcinomas: Correlation with Metastasis and Angiogenesis. Turk patoloji dergisi. 2014. Epub 2014/10/11. Metastaz Iliskili Protein 1 Ekspresyonunun Oral Skuamoz Hucreli Karsinomlarda Metastaz ve Anjiyogenez ile Iliskisi.
33. Kumar R, Wang RA, Mazumdar A, Talukder AH, Mandal M, Yang Z, et al. A naturally occurring MTA1 variant sequesters oestrogen receptor-alpha in the cytoplasm. Nature. 2002;418(6898):654-7.
34. Li W, Zhu H, Bao W, Fu H, Li Z, Liu X, et al. Involvement of metastasis tumor antigen 1 in hepatic regeneration and proliferation. Cellular physiology and biochemistry: international journal of experimental cellular physiology, biochemistry, and pharmacology 2008;22(1-4):315-26.
35. Li W, Ma L, Zhao J, Liu X, Li Z, Zhang Y. Expression profile of MTA1 in adult mouse tissues. Tissue & cell 2009;41(6):390-9.
36. Li G, Miles A, Line A, Rees RC. Identification of tumour antigens by serological analysis of cDNA expression cloning. Cancer immunology, immunotherapy : CII 2004;53(3):139-43.