J Korean Assoc Oral Maxillofac Surg.  2010 Dec;36(6):453-459.

Methylation of p16 and E-cadherin in ameloblastoma

• Park CW
• Yoon HK
• Park SJ

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.

Keyword

p16 genes; Cadherins; Methylation; Ameloblastoma

MeSH Terms

Ameloblastoma
Ameloblasts
Cadherins
Cell Adhesion Molecules
Cell Cycle
CpG Islands
Genes, p16
Methylation
Phenotype
Polymerase Chain Reaction
Recurrence
Cadherins
Cell Adhesion Molecules

Figure

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  Fig. 1. Bisulfite genomic sequencing result of 5'CpG island of the p16 gene.

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  Fig. 2. SSCP analysis of the p16 gene in ameloblastoma. Lane 1, 3, 4, 5 show corresponding band to C+, C++ line. (BL: blank, C+, C++: positive cell line, N/C: negative control, SSCP: single strand conformational polymorphism)

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  Fig. 3. Bisulfite genomic sequencing result of 5'CpG island of the E-cadherin gene.

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  Fig. 4. SSCP analysis of the E-cadherin gene in ameloblastoma. Lane 2 shows corresponding band to C+ line. (BL: blank, C+: positive cell line, N/C: negative control, SSCP: single strand conformational polymorphism)

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  Fig. 5. Loss of p16 expression in benign ameloblastoma without recurrence (upper) and with recurrence (middle), and carcinoma ex-ameloblastoma (lower).

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  Fig. 6. Loss of E-cadherin expression in benign ameloblastoma without recurrence (1st lane) and with recurrence (2nd lane), and in carcinoma ex-ameloblastoma (3rd and 4th lane).

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