Metastasis-Associated Protein 1 Expression in Oral Squamous Cell Carcinomas: Correlation with Metastasis and Angiogenesis / Metastaz İlişkili Protein 1 Ekspresyonunun Oral Skuamöz Hücreli Karsinomlarda Metastaz ve Anjiyogenez ile İlişkisi

Open access


Objective: Metastasis-associated protein 1 (MTA1) has been associated with poor prognosis in several carcinomas. Recent investigation has found that in different tumors, MTA1 protein significantly correlates with tumor angiogenesis, suggesting that MTA1 may be a possible angiogenesis-promoting molecule in malignant tumors. Thus, the current study was performed to determine the role of MTA1 protein in the biological behavior of oral squamous cell carcinoma and its relation with tumor angiogenesis.

Material and Method: In this study, 44 oral squamous cell carcinomas and 15 normal epitheliums were reviewed by IHC staining for MTA1 and CD105.

Results: Frequency of MTA1 expression in SCCs was recorded as 97.7%, which was significantly higher than that of the control group (33.3%). Mean percentage of MTA1 expression in oral squamous cell carcinomas was 76.88 ± 25.33% which was significantly higher than that of the control group (22.81 ±10.83). Our data showed a correlation between MTA1 expression with lymph node metastasis, tumor size and, stage. Evaluation of the correlation between MTA1 protein expression and micro vessel density showed that high micro vessel density was detected more frequently in tumors with MTA1 protein overexpression than in those without overexpression.

Conclusion: In the present study, high expression of the MTA1 protein was seen in oral squamous cell carcinoma, and was closely associated with tumor progression and increased tumor angiogenesis. The findings may indicate that MTA1 protein has clinical potentials as a useful indicator of progressive phenotype, a promising prognostic predictor to identify patients with poor prognosis and may be a potential novel therapeutic target of anti-angiogenesis for patients with oral squamous cell carcinoma.

1. Neville BW, Damm DD, Allen CM, Bouqout JE: Oral and maxillofacial pathology. 3rd ed. Philadelphia: Saunders; 2002. 317-36.

2. Ghanta KS, Li DQ, Eswaran J, Kumar R. Gene profiling of MTA1 identifies novel gene targets and functions. PloS One. 2011;6: e17135.

3. Law S, Kwong DL, Kwok KF, Wong KH, Chu KM, Sham JS, Wong J. Improvement in treatment results and long-term survival of patients with esophageal cancer: Impact of chemoradiation and change in treatment strategy. Ann Surg. 2003;238:339-47; discussion 347-8.

4. Li SH, Tian H, Yue WM, Li L, Gao C, Li WJ, Hu WS, Hao B. Metastasis-associated protein 1 nuclear expression is closely associated with tumor progression and angiogenesis in patients with esophageal squamous cell cancer. World J Surg. 2012; 36:623-31.

5. Shih CH, Ozawa S, Ando N, Ueda M, Kitajima M. Vascular endothelial growth factor expression predicts outcome and lymph node metastasis in squamous cell carcinoma of the esophagus. Clin Cancer Res. 2000;6:1161-8.

6. Toh Y, Oki E, Oda S, Tokunaga E, Ohno S, Maehara Y, Nicolson GL, Sugimachi K. Overexpression of the MTA1 gene in gastrointestinal carcinomas: correlation with invasion and metastasis. Int J Cancer. 1997; 74:459-63.

7. Toh Y, Nicolson GL. The role of the MTA family and their encoded proteins in human cancers: Molecular functions and clinical implications. Cli Exp Metastasis. 2009;26:215-27.

8. Kidd M, Modlin IM, Mane SM, Camp RL, Eick G, Latich I. The role of genetic markers-NA P1L1, MAGE-D2, and MTA1-in defining small-intestinal carcinoid neoplasia. Ann Surg Oncol. 2006;13:253-62.

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. Clin Exp Metastasis. 2003;20:19-24.

10. Yan C, Wang H, Toh Y, Boyd DD. Repression of 92-kDa type IV collagenase expression by MTA1 is mediated through direct interactions with the promoter via a mechanism, which is both dependent on and independent of histone deacetylation. J Biol Chem. 2003;278:2309-16.

11. 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. Int J Oral Maxillofac Surg. 2008;37:1039-46.

12. Eskens FA. Angiogenesis inhibitors in clinical development; Where are we now and where are we going? Br J Cancer. 2004;90: 1-7.

13. Kerbel R, Folkman J. Clinical translation of angiogenesis inhibitors. Nat Rev Cancer. 2002;2:727-39.

14. Florence ME, Massuda JY, Brocker EB, Metze K, Cintra ML, Souza EM. Angiogenesis in the progression of cutaneous squamous cell carcinoma: An immunohistochemical study of endothelial markers. Clinics (Sao Paulo). 2011;66:465-8.

15. Marioni G, Ottaviano G, Giacomelli L, Staffieri C, Casarotti- Todeschini S, Bonandini E Staffieri A, Blandamura S. CD105- assessed micro-vessel density is associated with malignancy recurrence in laryngeal squamous cell carcinoma. Eur J Surg Oncol. 2006;32:1149-53.

16. Zvrko E, Mikic A, Vuckovic L. Clinicopathologic significance of CD105-assessed microvessel density in glottic laryngeal squamous cell carcinoma. Auris Nasus Larynx. 2010;37:77-83.

17. Li SL, Gao DL, Zhao ZH, Liu ZW, Zhao QM, Yu JX, Chen KS, Zhang YH. Correlation of matrix metalloproteinase suppressor genes RECK, VEGF, and CD105 with angiogenesis and biological behavior in esophageal squamous cell carcinoma. World J Gastroenterol. 2007;13:6076-81.

18. Li SH, Tian H, Yue WM, Li L, Li WJ, Chen ZT, Hu WS, Zhu YC, Qi L. Overexpression of metastasis-associated protein 1 is significantly correlated with tumor angiogenesis and poor survival in patients with early-stage non-small cell lung cancer. Ann Surg Oncol. 2011;18:2048-56.

19. Moon WS, Chang K, Tarnawski AS. Overexpression of metastatic tumor antigen 1 in hepatocellular carcinoma: Relationship to vascular invasion and estrogen receptor-alpha. Human Pathol. 2004;35:424-9.

20. Jang KS, Paik SS, Chung H, Oh YH, Kong G. MTA1 overexpression correlates significantly with tumor grade and angiogenesis in human breast cancers. Cancer Sci. 2006; 97:374-9.

21. Moon HE, Cheon H, Chun KH, Lee SK, Kim YS, Jung BK, Park JA, Kim SH, Jeong JW, Lee MS. Metastasis-associated protein 1 enhances angiogenesis by stabilization of HIF-1alpha. Oncology Rep. 2006;16:929-35.

22. Vermeulen PB, Gasparini G, Fox SB, Colpaert C, Marson LP, Gion M, Belien JA, de Waal RM, Van Marck E, Magnani E, Weidner N, Harris AL, Dirix LY. Second international consensus on the methodology and criteria of evaluation of angiogenesis quantification in solid human tumours. Eur J Cancer. 2002;38:1564-79.

23. 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 J Surg. 2009;33:1876-81.

24. Margaritescu C, Simionescu C, Mogoanta L, Badea P, Pirici D, Stepan A, Ciurea R. Endoglin (CD105) and microvessel density in oral squamous cell carcinoma. Rom J Morphol Embryol. 2008;49:321-6.

25. Schimming R, Marme D. Endoglin (CD105) expression in squamous cell carcinoma of the oral cavity. Head Neck. 2002;24:151-6.

26. Eshghyar N, Mohammadi N, Rahrotaban S, Motahhary P, Vahedi Vaez SM. Endoglin (CD105) positive microvessel density and its relationship with lymph node metastasis in squamous cell carcinoma of the tongue. Arch Iran Med. 2011; 14:276-80.

27. Margaritescu C, Pirici D, Stinga A, Simionescu C, Raica M, Mogoanta L, Stepan A, Ribatti D. VEGF expression and angiogenesis in oral squamous cell carcinoma: An immunohistochemical and morphometric study. Clin Exp Med. 2010;10:209-14.

28. Miyahara M, Tanuma J, Sugihara K, Semba I. Tumor lymphangiogenesis correlates with lymph node metastasis and clinicopathologic parameters in oral squamous cell carcinoma. Cancer. 2007;110:1287-94.

29. Chien CY, Su CY, Hwang CF, Chuang HC, Hsiao YC, Wu SL, Huang CC. Clinicopathologic significance of CD105 expression in squamous cell carcinoma of the hypopharynx. Head Neck. 2006;28:441-6.

30. Kyzas PA, Cunha IW, Ioannidis JP. Prognostic significance of vascular endothelial growth factor immunohistochemical expression in head and neck squamous cell carcinoma: A metaanalysis. Clin Cancer Res. 2005;11:1434-40.

31. Martone T, Rosso P, Albera R, Migliaretti G, Fraire F, Pignataro L, Pruneri G, Bellone G, Cortesina G. Prognostic relevance of CD105+ microvessel density in HNSCC patient outcome. Oral Oncol. 2005;41:147-55.

32. Kademani D. Oral cancer. Mayo Clin Pro. 2007;82:878-87.

33. Chen HY, Yu SL, Chen CH, Chang GC, Chen CY, Yuan A, Cheng CL, Wang CH, Terng HJ, Kao SF, Chan WK, Li HN, Liu CC, Singh S, Chen WJ, Chen JJ, Yang PC. A five-gene signature and clinical outcome in non-small-cell lung cancer. N Engl J Med. 2007;356:11-20.

34. D’Amico TA. Angiogenesis in non-small cell lung cancer. Semin Thorac Cardiovasc Surg. 2004;16:13-8.

35. Manavathi B, Singh K, Kumar R. MTA family of coregulators in nuclear receptor biology and pathology. Nucl Recept Signal. 2007;5:e010.

36. Guo NL, Wan YW, Tosun K, Lin H, Msiska Z, Flynn DC, Remick SC, Vallyathan V, Dowlati A, Shi X, Castranova V, Beer DG, Qian Y. Confirmation of gene expression-based prediction of survival in non-small cell lung cancer. Clin Cancer Res. 2008;14:8213-20.

37. Denslow SA, Wade PA. The human Mi-2/NuRD complex and gene regulation. Oncogene. 2007;26:5433-8.

38. Mazumdar A, Wang RA , Mishra SK, Adam L, Bagheri-Yarmand R, Mandal M, Vadlamudi RK, Kumar R. Transcriptional repression of oestrogen receptor by metastasis-associated protein 1 corepressor. Nat Cell Biol. 2001;3:30-7.

39. Manavathi B, Kumar R. Metastasis tumor antigens, an emerging family of multifaceted master coregulators. J Biol Chem. 2007;282:1529-33.

Turkish Journal of Pathology

The Journal of Federation of Turkish Pathology Societies 

Journal Information

Cite Score 2017: 0.74

SCImago Journal Rank (SJR) 2017: 0.286
Source Normalized Impact per Paper (SNIP) 2017: 0.674


All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 149 149 6
PDF Downloads 71 71 4