Ameloblastic carcinoma ex ameloblastoma: report of a case–possible involvement of CpG island hypermethylation of the p16 gene in malignant transformation

Yoon

J Korean Assoc Oral Maxillofac Surg

2010

(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 ...

Section: ⅳ Discussionmentioning

confidence: 95%

“…Abiko et al reported that hypermethylation of p16 may have been involved in the malignant transformation of the ameloblastoma in the present case. Hypermethylation of CpG islands of the p16 gene was detected in the malignant parts of the tumor 8 .…”

Section: ⅰ Introductionmentioning

confidence: 99%

Methylation of p16 and E-cadherin in ameloblastoma

Yoon

J Korean Assoc Oral Maxillofac Surg

2010

International Journal of Oral and Maxillofacial Surgery

“…Due to freshness of the sample, RNA was extracted and cDNA was synthesized. According to Dr. Carcinci's article and due to PKM2 and MAPK8IP2 genes mutations report in esophagus, breast and kidney cancers (24,26,27) The techniques and the size of samples may also be changed to improve these investigations. As the PCR-RFLP method has been used in this study, we cannot exclude consequently any nucleotide changes outside the recognition sequences of the restriction enzymes used, in the corresponding genes.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Pkm2 and Mapk8ip2 polymorphism in ameloblastic carcinoma: a retrospective quantitative study

Jahangirnia

Akhlaghi

Ghaderian

et al. 2013

Ameloblastic carcinoma (AC) is a rare malignant epithelial odontogenic tumor that histologically retains the features of ameloblastic differentiation and exhibits cytological features of malignancy in the primary or recurrent tumor. It may develop within a preexisting ameloblastoma or arise de novo or from an odontogenic cyst. Epidemiological evidence shows that human cancer is generally caused by genotoxic factors, genes involved in the susceptibility of cancer, including those involved in metabolism or detoxification of genotoxic environment and those controlling DNA replication. Nowadays, gene polymorphism has an important role in development of malignant tumor .We report a case series study of ameloblastic carcinoma and ameloblastoma to show the role of PKM2 and MAPK8IP2 polymorphisms in these tumors. The DNA was extracted separately from specimens in paraffin sections of the tumor. Polymorphism of these genes was determined by PCR-RFLP (Polymerase Chain Reaction-Restriction fragment length polymorphism) method. The allele distributions of all samples were in Hardy-Weinberg equilibrium. The genotype and allele distribution in these genes were not statistically different between patients and controls.

“…Malignant behaviour of ameloblastomas with haematogenous dissemination is rare [12]. Malignant ameloblastomas are further classifi ed as metastasising ameloblastoma or the more aggressive ameloblastic carcinoma [6].…”

Section: Introductionmentioning

confidence: 99%

“…Malignant ameloblastomas are further classifi ed as metastasising ameloblastoma or the more aggressive ameloblastic carcinoma [6]. Ameloblastic carcinoma may arise de novo or as a transformation of a benign ameloblastoma [12]. In a report of 340 patients in a Brazilian population by Fernandes et al for odontogenic tumours between 1954 and 2004, 44% of cases, 150 patients, had ameloblastoma and one patient, 3%, had an ameloblastic carcinoma [4].…”

Section: Introductionmentioning

confidence: 99%

Ameloblastoma, a rare benign odontogenic tumour: an interesting tumour review targeting the role of radiation therapy

Koukourakis

Sotiropoulou-Lontou

2011

Clin Transl Oncol

Ameloblastoma is known as a benign, slow-growing, rare, odontogenic neoplasm. The solid/multicystic, the unicystic with a fibrous connective-tissue capsule and the peripheral ameloblastoma represent the three well distinguished clinical types of ameloblastoma. Surgical resection with an attempt to achieve adequate free margins constitutes a well documented and accepted treatment modality. Controversies exist, however, with regard to the extent of operative intervention. Patients with inadequate or positive surgical margins or unresectable lesions can be treated with radiation or combined radiation and chemotherapy. The authors present a review of this sparse disease focusing on the special role and efficacy of radiation therapy in its management.