Aberrant expression of p53, p16INK4a and Ki-67 as basic biomarker for malignant progression of oral leukoplakias
Aberrant expression of p53, p16INK4a and Ki-67 as basic biomarker for malignant progression of oral leukoplakias
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DOI：
10.1111/j.1600-0714.2011.01026.x
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发表时间：
2011-09-01
影响因子：
3.3
通讯作者：
Bosch, Franz X.
中科院分区：
文献类型：
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作者：
Nasser, Wasim;Flechtenmacher, Christa;Bosch, Franz X.
背景：口腔白斑伴或不伴发育不良的恶性进展的风险是不可预测的。材料与方法：采用免疫组化方法回顾性检测35例非发育不良的白斑、4例发育不良的白斑及肿瘤患者类似病变的pRb、p53、p16（INK4a）、Cyclin D1、Ki-67蛋白的表达。联合异常表达模式对无发育不良的白斑进展的预测能力进行了检查。结果：无发育不良的白斑患者中p53、Ki-67和Cyclin D1表达升高，p16（INK4a）缺失的比例分别为45.9%、38.9%、29.4%和32.4%。所有的改变都随着进展而增加，但阳性预测价值较差。然而，p53/p16(INK4a)/Ki-67联合畸变仅在3例（9%）病例中发生，其中2例（66.7%）进展为发育不良和原位癌。p53/p16(INK4a)/Ki-67联合改变阴性预测值（NPV）和敏感性为100%，特异性为97%，阳性预测值（PPV）为67%。相比之下，p53/p16(INK4a)/Cyclin D1联合改变的NPV为97%，敏感性为50%，特异性为90%，PPV仅为25%。没有观察到pRb的缺失和伴随的p16（INK4a）的过表达，这表明HPV与口腔白斑有关。结论：我们建议p53/p16(INK4a)/Ki-67联合改变作为诊断高危白斑患者的基础标志物。没有这种改变的病变似乎是无害的。未来的研究应该验证这些发现，并寻找能够进一步提高所提出的基本标记物PPV的蛋白质。口腔病理杂志，2011,40:629-635
BACKGROUND: The risk of malignant progression of oral leukoplakia with and without dysplasia is unpredictable.MATERIALS AND METHODS: Leukoplakias without dysplasia of 35 patients, leukoplakias with dysplasia of 4 patients, and similar lesions obtained from tumor patients were retrospectively examined by immunohistochemistry for the expression of the proteins pRb, p53, p16(INK4a), Cyclin D1 and Ki-67. The predictive power of combined aberrant expression patterns for the progression of leukoplakias without dysplasia was examined.RESULTS: Increased expression of p53, Ki-67 and Cyclin D1, and loss of p16(INK4a) occurred in 45.9%, 38.9%, 29.4% and 32.4% of the leukoplakias without dysplasia, respectively. All alterations increased with progression but had poor positive predictive value. However, the combined p53/p16(INK4a)/Ki-67 aberration occurred in only three (9%) cases, of which two patients (66.7%) experienced progression to dysplasia and carcinoma in situ. The combined p53/p16(INK4a)/Ki-67 alteration had a negative predictive value (NPV) and sensitivity of 100%, specificity of 97% and positive predictive value (PPV) of 67%. By contrast, the combined p53/p16(INK4a)/Cyclin D1 alteration had 97% NPV and sensitivity of 50%, specificity of 90% and only 25% PPV. Loss of pRb and concomitant overexpression of p16(INK4a) were not observed arguing against an involvement of HPV in oral leukoplakia.CONCLUSIONS: We propose the combined p53/p16(INK4a)/Ki-67 alteration as a basic marker to define high risk leukoplakia patients. Lesions not showing this alteration appear to be harmless. Future studies should validate these findings and search for proteins which can further improve the PPV of the proposed basic marker. J Oral Pathol Med (2011) 40: 629-635