Pavelic Z P, Lasmar M, Pavelic L, Sorensen C, Stambrook P J, Zimmermann N, Gluckman J L
Department of Otolaryngology Head and Neck Surgery, University of Cincinnati, Ohio 45267-0528, USA.
Eur J Cancer B Oral Oncol. 1996 Sep;32B(5):347-51. doi: 10.1016/0964-1955(96)00025-5.
Oral cavity cancer is a major health concern worldwide. Despite advances in surgery, radiotherapy and chemotherapy over the past 35 years, there has been no significant enhancement in the survival of oral cavity cancer patients. Improved survival will require identification of reliable prognostic markers that provide a rational basis for assessment of risk for progression. The altered retinoblastoma (RB) gene has been linked to the hereditary retinoblastoma. This gene is defective in several types of human malignancies. The intent of this study was to evaluate the role of the RB gene in oral cavity tumorigenesis and to explore whether or not there is a relationship between the loss of RB protein and each of several clinicopathological parameters in oral cavity carcinomas. We have analysed the expression of the RB gene in four cell lines (J82, ML1, SaOS2 and WERI-RB-1), 182 oral cavity carcinomas (75 T1 and 107 T3 and T4 lesions) and 55 normal tissues adjacent to cancer by means of an immunohistochemical method and Western immunoblotting. The expression of RB protein was then correlated with clinical outcome in the patients with primary tumours. The significantly higher rate of altered RB expression was found in advanced oral cavity tumours (40 of 107; 37%) in comparison with low grade tumours (9 of 75; 7%). In T3 and T4 tumours, RB gene expression did not correlate with presence or absence of lymph node metastasis, degree of differentiation and patient survival. However, in the T1 cohort, poorer survival rate was seen for those patients who had a tumour with loss of RB protein. This study suggests that tumours in which the RB protein was altered were more aggressive than tumours in which the RB protein was present and that loss of RB protein in oral cavity cancer may be a prognostic variable of tumour progression.
口腔癌是全球主要的健康问题。尽管在过去35年里手术、放疗和化疗取得了进展，但口腔癌患者的生存率并没有显著提高。提高生存率需要识别可靠的预后标志物，为评估进展风险提供合理依据。视网膜母细胞瘤（RB）基因改变与遗传性视网膜母细胞瘤有关。该基因在几种人类恶性肿瘤中存在缺陷。本研究的目的是评估RB基因在口腔肿瘤发生中的作用，并探讨RB蛋白缺失与口腔癌的几种临床病理参数之间是否存在关系。我们通过免疫组织化学方法和Western免疫印迹分析了RB基因在四种细胞系（J82、ML1、SaOS2和WERI-RB-1）、182例口腔癌（75例T1期和107例T3和T4期病变）以及55例癌旁正常组织中的表达。然后将RB蛋白的表达与原发性肿瘤患者的临床结果进行关联。与低级别肿瘤（75例中的9例；7%）相比，在晚期口腔肿瘤（107例中的40例；37%）中发现RB表达改变的发生率显著更高。在T3和T4肿瘤中，RB基因表达与有无淋巴结转移、分化程度和患者生存率无关。然而，在T1队列中，RB蛋白缺失的肿瘤患者生存率较低。本研究表明，RB蛋白改变的肿瘤比RB蛋白存在的肿瘤更具侵袭性，口腔癌中RB蛋白缺失可能是肿瘤进展的一个预后变量。
