The study of p62/SQSTM1 as a malignant transformation marker for oral potentially malignant disorders and a prognostic marker for oral squamous cell carcinoma

• Main Authors: Nan-En Ho, 何念恩
• Other Authors: 陳信銘
• Format: Others
• Language: en_US
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/07213698655090136318

碩士 === 國立臺灣大學 === 臨床牙醫學研究所 === 101 === Background Oral potentially malignant disorders (OPMDs) were lesions that have a risk of transformation into oral cancer. Up to date, there is no any reliable method to predict malignant transformation of OPMD to be oral cancer, therefore, no consensus on how to treat OPMDs has been established. The aim of this study was to find a marker that can predict the malignant transformation potential of OPMDs and the prognosis of oral squamous cell carcinomas (OSCCs). Materials and methods The present study enrolled 57 patients with histology-proved OPMDs that further progress into OSCCs at National Taiwan University Hospital. We also recruited 63 patients with histology-proved OPMDs with no malignant transformation into oral cancer; 88 OSCC specimens as well as 20 normal mucosa tissues as the control groups. Immunohistochemical examination of p62/SQSTM1 was tested in these samples. The patients’ clinicopathological parameters were recorded and compared with their different expressions of p62. Kaplan-Meier graphs and Cox proportional hazard model were used for survival analysis. Results There were totally 208 patients enrolled in this study, including 20 normal controls, 57 progressing OPMDs, 63 non-progressing OPMDs, and 88 OSCCs. The expression pattern of p62 was significantly different between progress and non-progress OPMD groups. OPMDs with higher cytoplasmic p62 expression or lower nuclear immunoactivity exhibited greater malignant transformation potentiality and shorter transformation interval. Besides, the expression of p62 was highly discovered in oral cancer specimens than normal tissues or OPMDs. The cytoplasmic expression of p62 was related to tumor size (p=0.042), neck metastasis (p=0.032), and TNM stage (p=0.009). The high expression of p62 in cytoplasm also correlated with poor 5-year survival rate of OSCC patients (p=0.002). By Cox proportional hazard model, the hazard ratio of cytoplasmic p62 was 4.2 (95%CI, 1.495-11.833). Conclusion p62/SQSTM1 is a potential marker that can predict the malignant transformation of OPMDs. The accumulation of p62 expression in cytoplasm as well as negative expression in nucleus implies higher malignant transformation potentiality of OPMDs. In addition, p62 aggregates in cytoplasm is correlated with poor prognosis of OSCC patients.