p62/SQSTM1作為口腔癌前病變惡性轉變之標記因子及口腔癌之預後因子之研究

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

何念恩(Nan-En Ho)

指導教授 ： 陳信銘

國立臺灣大學/牙醫專業學院/臨床牙醫學研究所/碩士(2013年)

https://doi.org/10.6342/NTU.2013.00226

摘要

背景
口腔癌前病變指的是有可能發展為口腔癌的病灶。然而由於缺乏預測其惡性轉變潛能的能力，直至目前為止對於口腔癌前病變的治療仍沒有共識。本實驗之目的在於找出能同時預測口腔癌前病變之惡性轉變潛能及口腔癌預後的因子。
實驗方法
本實驗蒐集57例在台大醫院經切片確診為口腔癌前病變並進一步發展成為口腔癌的病人。同時隨機選取63例切片確診為口腔癌前病變卻並未轉變成為口腔癌的病人做為對照。另外有20個正常黏膜組織及88例口腔癌的樣本一同研究。在這些組織中，我們使用免疫組織化學染色來試驗p62/SQSTM1的表現。病人的臨床及病理資料經整理後與p62的表現做比較。採用Kaplan-Meier graphs及Cox proportional hazard model進行存活分析。
結果
本實驗共蒐集了208例個案，包含20個正常的對照組，57個有轉變的口腔癌前病變，63個未轉變的口腔癌前病變及88例口腔癌。p62的表現形式在兩組口腔癌前病變的病人中有很大的不同。在具有較高p62細胞質表現或較低的細胞核表現的口腔癌前病變組織中，存在有較高的惡性轉變潛能及較短的惡性轉變時間。此外，p62的表現在口腔癌中顯著大於正常組織或口腔癌前病變。p62在細胞質的表現與腫瘤的大小，頸部淋巴轉移及腫瘤TNM分期相關(p值分別為0.042，0.032，0.009)。p62在細胞質中的高表現與口腔癌病人的5年存活率相關(p值為0.002)。經由Cox proportional hazard model，細胞質的p62表現之風險比為4.2(95%信頼區間為1.495-11.833)。
結論
p62/SQSTM1可作為預測口腔癌前病變之惡性轉變潛能的因子。細胞質中累積的p62及細胞核中沒有p62的表現顯示口腔癌前病變帶有較高的惡性轉變潛能。另一方面，p62在細胞質中的聚積也與口腔癌病人較差的預後相關。

關鍵字

口腔癌前病變 ； 口腔癌 ； 惡性轉變 ； p62/SQSTM1

並列摘要

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.

並列關鍵字

oral potentially malignant disorders ； oral squamous cell carcinoma ； malignant transformation ； p62/SQSTM1

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