DOI QR코드

DOI QR Code

Methylation of p16 and E-cadherin in ameloblastoma

법랑아세포종에서 p16과 E-cadherin의 메틸화

  • Park, Can-Woong (Department of Oral and Maxillofacial Surgery, Pusan Paik Hospital, College of Medicine, Inje University) ;
  • Yoon, Hye-Kyoung (Department of Pathology, Pusan Paik Hospital, College of Medicine, Inje University) ;
  • Park, Sang-Jun (Department of Oral and Maxillofacial Surgery, Pusan Paik Hospital, College of Medicine, Inje University)
  • Received : 2010.07.06
  • Accepted : 2010.12.10
  • Published : 2010.12.31

Abstract

Introduction: Ameloblastic carcinoma is a rare malignant lesion, and may arise from either carcinoma ex-ameloblastoma or de novo carcinoma. Aberrant promoter hypermethylation of the tumor-associated genes leading to their inactivation is a common event in many cancer types. The p16/CDKN2/INK4A gene and p16 5 protein are involved directly in regulating the cell cycles. Cadherins are cell adhesion molecules that modulate the epithelial phenotype and regulate tumor invasion. The aim of this study was to evaluate the roles of p16 and E-cadherin methylation and loss of p16 and E-cadherin expression in the malignant transformation of an ameloblastoma. Materials and Methods: Eight cases of ameloblastoma, including 4 benign ameloblastomas without recurrence, 2 benign ameloblastomas with recurrence and 2 carcinoma ex-ameloblastomas, were examined. The promoter hypermethylation profile of the p16 and E-cadherin genes was studied using methylation-specific polymerase chain reaction (MSP) and immunohistochemical staining for p16 and E-cadherin expression. Results: 1) Aberrant CpG island methylation of the p16 gene was detected in 3 of the 4 benign ameloblastomas without recurrence and 1 of the 2 benign ameloblastomas with recurrence. 2) Aberrant CpG island methylation of the E-cadherin gene was found in 1 of the 4 benign ameloblastomas without recurrence. 3) A loss of p16 expression was noted in 1 of 4 benign ameloblastomas without recurrence and 1 of 2 carcinoma ex-ameloblastomas. 4) A loss of E-cadherin expression was noted in 2 of the 4 benign ameloblastomas without recurrence, 1 of the 2 benign ameloblastomas with recurrence and 2 of the 2 carcinoma ex-ameloblastomas. 5) A loss of p16 expression was observed in 1 of the 4 cases showing aberrant methylation of the p16 gene. 6) A loss of E-cadherin expression was observed in 3 benign ameloblastoma case showing aberrant methylation of the E-cadherin gene. Conclusion: These results suggest that loss of E-cadherin expression related to the other genetic pathway (not methylation) might be an adjuvant indicator predicting the malignant transformation of an ameloblastoma. However, the number of samples in this study was too small and the relationship between the treatment methods and clinical course were not defined. Therefore, further study will be needed.

Keywords

References

  1. Barnes L, Eveson JW, Reichart P, Sidransky D, eds. World Health Organization classification of tumours: pathology and genetics of head and neck tumours. Lyon, France: International Agency for Research on Cancer Press; 2005.
  2. Baylin SB, Esteller M, Rountree MR, Bachman KE, Schuebel K, Herman JG. Aberrant patterns of DNA methylation, chromatin formation and gene expression in cancer. Hum Mol Genet 2001; 10:687-92. https://doi.org/10.1093/hmg/10.7.687
  3. French SW, Dawson DW, Miner MD, Doerr JR, Malone CS, Wall R, et al. DNA methylation profiling: a new tool for evaluating hematologic malignancies. Clin Immunol 2002;103:217-30. https://doi.org/10.1006/clim.2002.5186
  4. Ho A, Dowdy SF. Regulation of G(1) cell-cycle progression by oncogenes and tumor suppressor genes. Curr Opin Genet Dev 2002;12:47-52. https://doi.org/10.1016/S0959-437X(01)00263-5
  5. Rush LJ, Plass C. Alterations of DNA methylation in hematologic malignancies. Cancer Lett 2002;185:1-12. https://doi.org/10.1016/S0304-3835(02)00288-4
  6. Kresty LA, Mallery SR, Knobloch TJ, Song H, Lloyd M, Casto BC, et al. Alterations of p16(INK4a) and p14(ARF) in patients with severe oral epithelial dysplasia. Cancer Res 2002:62:5295-300.
  7. Viswanathan M, Tsuchida N, Shanmugam G. Promoter hypermethylation profile of tumor-associated genes p16, p15, hMLH1, MGMT and E-cadherin in oral squamous cell carcinoma. Int J Cancer 2003;105:41-6. https://doi.org/10.1002/ijc.11028
  8. Abiko Y, Nagayasu H, Takeshima M, Yamazaki M, Nishimura M, Kusano K, et al. Ameloblastic carcinoma ex-ameloblastoma: report of a case-possible involvement of CpG island hypermethylation of the p16 gene in malignant transformation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;103:72-6. https://doi.org/10.1016/j.tripleo.2006.01.021
  9. Chen Q, Lipkina G, Song Q, Kramer RH. Promoter methylation regulates cadherin switching in squamous cell carcinoma. Biochem Biophys Res Commun 2004;315:850-6. https://doi.org/10.1016/j.bbrc.2004.01.143
  10. Pho SW, Kim YS, Park JY, Kim CH, Lee W, Park MK. The hypermethylation of E-cadherin gene in oral squamous cell carcinoma. J Korean Assoc Oral Maxillofac Surg 2008;34:135-40.
  11. Auerkari EI. Methylation of tumor suppressor genes p16(INK4a), p7(Kip1) and E-cadherin in carcinogenesis. Oral Oncol 2006;42:5-13. https://doi.org/10.1016/j.ooe.2005.05.007
  12. SSastre J, Munnoz M, Naval L, Adrados M. Ameloblastic carcinoma of the maxilla: report of a case. J Oral Maxillofac Surg 2002;60: 102-4. https://doi.org/10.1053/joms.2002.29086
  13. Verneuil A, Sapp P, Huang C, Abemayor E. Malignant ameloblastoma: classification, diagnostic and therapeutic challenges. Am J Otolaryngol 2002;23:44-8. https://doi.org/10.1053/ajot.2002.28769
  14. Thoma KH. Oral pathology: a histological, roentgenological, and clinical study of the diseases of the teeth, jaws, and mouth. 3rd ed. St. Louis: Mosby; 1950.
  15. Pindborg JJ, Kramer I, Torloni H. Histological typing of odontogenic tumors, jaw cysts, and allied lesions. Geneva, Switzerland: World Health Organization; 1972.
  16. Slootweg PJ, Muller H. Malignant ameloblastoma or ameloblastic carcinoma. Oral Surg Oral Med Oral Pathol 1984;57:168-76. https://doi.org/10.1016/0030-4220(84)90207-X
  17. Zhao Y, Zhang S, Fu B, Xiao C. Abnormalities of tumor suppressor genes P16 and P15 in primary maxillofacial squamous cell carcinomas. Cancer Genet Cytogenet 1999;112:26-33. https://doi.org/10.1016/S0165-4608(98)00259-3
  18. Nodit L, Barnes L, Childers E, Finkelstein S, Swalsky P, Hunt J. Allelic loss of tumor suppressor genes in ameloblastic tumors. Mod Pathol 2004;17:1062-7. https://doi.org/10.1038/modpathol.3800147