Cruz I B, Snijders P J, Meijer C J, Braakhuis B J, Snow G B, Walboomers J M, van der Waal I
Department of Pathology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
J Pathol. 1998 Apr;184(4):360-8. doi: 10.1002/(SICI)1096-9896(199804)184:4<360::AID-PATH1263>3.0.CO;2-H.
Epithelial dysplasia is usually used to establish the prognosis of oral premalignant lesions. Its assessment, however, is subjective and does not always correctly predict the outcome of the lesions in terms of malignant transformation. Early molecular alteration(s) that dictate the development of cancer should be identified and used to evaluate oral premalignant lesions. In this context, alterations in the expression of p53 were investigated. Thirty-five oral premalignant lesions and 11 carcinomas that developed from them in a period of 16 years were investigated for p53 expression by immunohistochemistry. Normal oral mucosa from healthy individuals and oral benign lesions were used as controls. In benign lesions and normal mucosa, p53 staining, when present, was confined to the basal cell layer. Seven out of 35 (20 per cent) premalignant lesions showed p53 expression clearly above the basal cell layer and six of these (86 per cent) developed carcinomas. Suprabasal p53 expression was found in three lesions with no or mild dysplasia that developed carcinomas. All carcinomas derived from premalignant lesions with p53 suprabasal expression showed p53 expression in neoplastic cells. The combined use of histological parameters (presence of moderate or severe dysplasia) with p53 expression patterns (p53 staining above the basal cell layer) showed the highest sensitivity for the detection of lesions that progressed to carcinoma (91 per cent). When used individually, the p53 expression pattern showed higher specificity than assessment of dysplasia (96 per cent vs. 54 per cent) and higher positive predictive value (86 per cent vs. 44 per cent) for correct prediction of the malignant transformation of the lesions. The results suggest that clear expression of p53 above the basal cell layer is an early event in oral carcinogenesis and an indicator of a developing carcinoma, even preceding morphological tissue alterations. However, since immunohistochemistry cannot always detect changes in p53 expression in lesions preceding carcinoma, p53 immunohistochemical analysis is strongly recommended in conjunction with histological parameters, to increase the sensitivity of detection of cases that will progress to carcinoma.
上皮发育异常通常用于判断口腔癌前病变的预后。然而，其评估具有主观性，并且在预测病变恶变结果方面并不总是准确无误。应当识别出那些决定癌症发展的早期分子改变，并将其用于评估口腔癌前病变。在此背景下，对p53表达的改变进行了研究。通过免疫组织化学法，对35例口腔癌前病变以及在16年期间由这些病变发展而来的11例癌进行了p53表达情况的调查。选取健康个体的正常口腔黏膜和口腔良性病变作为对照。在良性病变和正常黏膜中，若存在p53染色，则仅限于基底细胞层。35例（20%）癌前病变中有7例显示p53表达明显高于基底细胞层，其中6例（86%）发展为癌。在3例无或轻度发育异常且发展为癌的病变中发现了基底上层p53表达。所有源自具有基底上层p53表达的癌前病变的癌，其肿瘤细胞均显示p53表达。将组织学参数（中度或重度发育异常的存在情况）与p53表达模式（基底细胞层以上的p53染色）结合使用，对于检测进展为癌的病变具有最高的敏感性（91%）。单独使用时，p53表达模式比发育异常评估具有更高的特异性（分别为96%和54%）以及更高的阳性预测值（分别为86%和44%），能够正确预测病变的恶变。结果表明，基底细胞层以上p53的清晰表达是口腔癌发生过程中的早期事件，也是癌发展的一个指标，甚至早于形态学组织改变。然而，由于免疫组织化学法并非总能检测到癌前病变中p53表达的变化，因此强烈建议将p53免疫组织化学分析与组织学参数结合使用，以提高对将进展为癌的病例的检测敏感性。
