Cruz I B, Meijer C J, Snijders P J, Snow G B, Walboomers J M, van Der Waal I
Department of Pathology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
J Pathol. 2000 Jun;191(2):132-7. doi: 10.1002/(SICI)1096-9896(200006)191:2<132::AID-PATH605>3.0.CO;2-E.
p53 is a tumour suppressor gene encoding a protein whose function is impaired in a very large proportion of human cancers. The objectives of this study were to determine the natural history of p53 alterations during stages of oral carcinogenesis, by comparing p53 immunoexpression in oral squamous cell carcinomas (OSCCs), their non-malignant adjacent mucosa, and respective metastases; and to define the potential practical consequences for clinical management of p53 staining in the non-malignant adjacent mucosa. Forty-two samples of non-malignant mucosa adjacent to OSCCs, the respective carcinomas, and six lymph node metastases derived from six of the OSCCs were investigated for p53 protein expression by immunohistochemistry. Seven out of 42 (17%) non-malignant mucosal samples immediately adjacent to OSCC showed suprabasal p53 staining and this was significantly associated with moderate/severe dysplasia (p=0.02). In six of these cases (86%), the respective carcinoma showed p53 immunoexpression in more than 50% of the neoplastic cells and in the remaining case, p53 immunoexpression was found in more than 25% of the neoplastic cells. In all p53-negative carcinomas that showed p53 immunoexpression in the non-malignant adjacent mucosa, p53 staining was never detected above the basal cell layer. Lymph node metastases showed the same patterns of p53 immunoexpression as the carcinomas from which they were derived. When suprabasal p53 staining is present in non-malignant mucosa immediately adjacent to OSCCs, this suggests stable p53 alterations which are maintained upon progression to overt malignancy. The immunostaining in non-malignant mucosa of the resection margins of OSCCs might be a valuable predictor for local recurrences and may therefore have implications for the management of patients who have received surgical treatment for OSCC.
p53是一种肿瘤抑制基因，编码一种在很大比例的人类癌症中功能受损的蛋白质。本研究的目的是通过比较口腔鳞状细胞癌（OSCC）、其非恶性相邻黏膜及各自转移灶中的p53免疫表达，来确定口腔癌发生各阶段p53改变的自然史；并明确非恶性相邻黏膜中p53染色对临床管理的潜在实际影响。通过免疫组织化学研究了42例OSCC相邻的非恶性黏膜样本、相应的癌组织以及6例OSCC的6个淋巴结转移灶中的p53蛋白表达。42例紧邻OSCC的非恶性黏膜样本中有7例（17%）显示基底上层p53染色，这与中度/重度发育异常显著相关（p = 0.02）。在其中6例（86%）中，相应的癌组织显示超过50%的肿瘤细胞有p53免疫表达，在其余1例中，超过25%的肿瘤细胞有p53免疫表达。在所有非恶性相邻黏膜有p53免疫表达的p53阴性癌组织中，在基底细胞层以上从未检测到p53染色。淋巴结转移灶显示出与它们所源自的癌组织相同的p53免疫表达模式。当紧邻OSCC的非恶性黏膜中存在基底上层p53染色时，这表明p53改变是稳定的，在发展为明显恶性肿瘤时仍保持。OSCC切除边缘非恶性黏膜中的免疫染色可能是局部复发的有价值预测指标，因此可能对接受OSCC手术治疗的患者的管理有影响。
