Methylation of p16 and E-cadherin in ameloblastoma

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.

A study on the expression of p16 gene, methylation of p16 gene promoter and HPV typing in uterine cervical neoplasia / 부인종양

OBJECTIVE: p16 is cyclin-dependent kinase (CDK) inhibitor which decelerates cell cycle by inactivating CDKs that phosphorylate retinoblastoma protein (pRb). In cervical carcinogenesis, abnormality of p16 gene such as methylation of p16 gene promoter was investigated as an important factor. The aims of our study are to investigate the expression of p16 gene, methylation of p16 gene promoter region, and HPV typing in uterine cervical neoplasia. METHODS: A total of 104 samples (CIN1, 30 CIN2,3 45, invasive cancer, 29) were included. Expression of p16 was analyzed by immunohistochemistry, methylation of p16 gene promoter region was analyzed with methylation specific polymerase chain reaction (MSP) and we examed the result of HPV DNA testing. RESULTS: 1. In high risk HPV and low risk or negative group, p16 gene expression was observed in CIN1 (30% vs 23%), CIN2, 3 (64% vs 58%) and in invasive cancer (80% vs 37%) respectively. In invasive cancer, p16 gene expression of high risk HPV group was statistically higher than that of low risk or negative group. 2. In high risk HPV and low risk or negative group, p16 promoter methylation was observed in CIN1 (23% vs 17%), CIN2, 3 (25% vs 47%) and in invasive cancer (19% vs 87%) respectively. In invasive cancer, p16 promoter methylation of low risk or negative HPV group was statistically higher than that of low risk or negative group. CONCLUSION: p16 gene expression would be marker for CIN and cancer. Methylation of p16 promoter region may be one of the important mechanism for uterine cervical carcinogenesis especially in negative or low risk HPV group. but further studies are needed to reinforce this statement.

Clinical Significance of p16 Protein Expression Loss and Aberrant p53 Protein Expression in Pancreatic Cancer

Pancreatic cancer is a disease with poor prognosis mainly due to low resection rates and late diagnosis. To increase resectability and improve survival rates, a better understanding of pancreatic cancer pathogenesis and more effective screening techniques are required. New methods, such as genetic and molecular alterations, may suggest novel approaches for pancreatic cancer diagnosis and treatment. We immunohistochemically investigated 44 formalin-fixed, paraffin-embedded specimens of pancreatic ductal adenocarcinoma using monoclonal anti-p16 antibodies and monoclonal anti-p53 antibodies. The expressions of p16 and p53 proteins were compared using the Chi-square test with SPSS. Disease-free survival was analyzed using the Kaplan-Meier method, verified by the Log- Rank test. Loss of p16 expression was noted in 20 (45.5%) cases and aberrant p53 protein expression was detected in 14 (31.8%) cases. Loss of p16 expression was associated with a higher incidence of lymph node metastasis (p=0.040) and a more advanced stage (p=0.015), although there was no significant correlation between p16 expression and survival. Aberrant p53 protein expression correlated with histologic grade (p= 0.038). Disease-free survival rate was significantly lower in the aberrant p53 protein positive group compared to the negative group (p=0.029). From our results, we suggest that p53 is not a prognostic factor; however, p16 and p53 genes do play important roles in the progression of pancreatic ductal adenocarcinoma.

Expression of P16 protein in oral verrucous carcinoma / 实用口腔医学杂志

Objective: To investigate the expression of P16 protein in oral verrucous carcinoma (VC) and oral squamous cell carcinoma (SCC) and to reveal its role in the occurrence and development of VC . Methods: Using streptavidin/peroxidase(SP) immunohistochemical technique(IHC) the expression of P16 protein in 41 samples, including 8 of normal mucosa (NM),13 VC,10 well differentiated squamous cell carcinoma (wdSCC),10 poorly differentiated squamous cell carcinoma (pdSCC) was studied.The average intensity score (IS) of immunohistochemical staining of the samples was calculated. Results: Weakly positive of P16 protein was obsereved in the 8 cases of NM. Positive expression was found in 10 of the 13 VC cases,8 of the 10 wdSCC and 6 of the 10 pdSCC.The IS in NM,VC, wd SCC and pdSCC was 0.4375?0.0498,1.5846?0.2681,0.9900?0.1894 and 0.8800?0.2590 respectively.The mean intensity of P16 protein in VC was higher than in wdSCC and pdSCC(P