Methylation of p16 and E-cadherin in ameloblastoma

Abstract

(J Korean Assoc Oral Maxillofac Surg 2010;36:453-9) Ⅰ. Introduction Ameloblastoma is the most common benign odontogenic tumor of the jaw, but local invasive growth or recurrence after the removal can be found. Ameloblastic carcinoma is rarely occurred and may arise as a result of malignant change in a pre-existing benign ameloblastoma (carcinoma ex-ameloblastoma) or as a primary ameloblastic carcinoma not preceded by ameloblastoma (de novo carcinoma)1 .In the malignant tumors, the gene mutation, epigene alterations such as hypermethylation of CpG islands of tumor suppressor gene may lead to suppression of transcription, which induces malignant transformation 2 . Methylation is one possible step towards DNA damage, and the same evolutionary pressure will favor all processes of silencing same genes in carcinogenesis 3,4 . The DNA methylation profile of cancer cells is characterized by global hypomethylation and simultaneous hypermethylation of selected CpG island gene promoters. Recently, the epigenetic phenomenon of DNA promoter methylation has gained increasing recognition as an important mechanism for transcriptional inactivation of cancer related genes. The identification of these methylation alterations and elucidation of the mechanistic events are important, as the methylation status of cancer cells can now be manipulated in vivo with demethylating chemotherapeutics 5 . Busan, 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. Methylation of p16 and E-cadherin in ameloblastoma3) 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 ...

Differential Expression of Immunohistochemical Markers in Ameloblastoma & Ameloblastic Carcinoma: A Systematic Review and Meta-analysis of observational studies

“…Moreover, there are a handful of studies on the proteins involved in the malignant transformation of AB to AC. 31 This review will help us understand the differential expression of immunohistochemical markers in AB and AC, as well as to evaluate the diagnostic potential of these markers in differentiating AC from AB. This systematic review included 19 comparative cross-sectional studies and evaluated the differences in clinical features and immunoexpression of nuclear, cytoplasmic, cell membrane, stromal, and proliferative markers between AB and AC.…”

“…Moreover, there are a handful of studies on the proteins involved in the malignant transformation of AB to AC. 31 This review will help us understand the differential expression of immunohistochemical markers in AB and AC, as well as to evaluate the diagnostic potential of these markers in differentiating AC from AB.…”