Thomson P J, Hamadah O, Goodson M L, Cragg N, Booth C
Oral & MaxilloFacial Surgery, School of Dental Sciences, Newcastle University, UK.
Br J Oral Maxillofac Surg. 2008 Jul;46(5):370-5. doi: 10.1016/j.bjoms.2008.01.003. Epub 2008 Feb 20.
Prediction of the behaviour of oral precancerous lesions (OPLs) is unreliable in clinical practice. The aim of this study was to analyse the efficacy of cell cyclin markers A and B1, and the proliferative marker Ki67, in predicting clinical outcome for patients with OPLs. A cohort of previously-treated patients with single OPLs were retrieved from the MaxilloFacial Dysplasia database and reviewed. All had dysplastic lesions excised by laser and were followed up for 5 years post-treatment. Outcome was determined as no recurrence or further disease. Excision specimens were re-examined immunohistochemically and labelling indices (LIs) for cyclin A, B1 and Ki67 determined. Forty patients, aged between 31 and 91 years, were recruited. There were no differences in age or sex. OPLs were predominantly leukoplakias on the floor of mouth or ventro-lateral tongue (65%), most of which exhibited moderate or severe dysplasia. Cyclin A LIs ranged from 3.9% to 31.3%, B1 0 to 28.3% and Ki67 3.5% to 54.5%. Using median LIs as 'cut off points' (12% cyclins; 22% Ki67) Kaplan-Meier survival analysis showed a significant risk of further progression of disease in patients with OPL LIs exceeding median values (Cyclin A p=0.02, Cyclin B1 p=0.01, Ki67 p=0.025). By combining analysis of both Cyclin A and B LI, the significance of the difference was increased (p<0.01). Cell cycle analysis is effective in identifying patients at risk of further progression of disease following treatment of OPLs. Multi-centre, longitudinal trials are needed to assess the precise role of cell cycle markers in their management.
在临床实践中,口腔癌前病变(OPL)行为的预测并不可靠。本研究的目的是分析细胞周期蛋白标志物A和B1以及增殖标志物Ki67在预测OPL患者临床结局方面的有效性。从颌面发育异常数据库中检索出一组先前接受过治疗的单发性OPL患者并进行回顾性分析。所有患者均通过激光切除发育异常病变,并在治疗后随访5年。结局判定为无复发或无进一步疾病。对切除标本进行免疫组织化学重新检查,并确定细胞周期蛋白A、B1和Ki67的标记指数(LI)。招募了40名年龄在31岁至91岁之间的患者。年龄和性别无差异。OPL主要为口底或舌腹外侧的白斑(65%),其中大多数表现为中度或重度发育异常。细胞周期蛋白A的LI范围为3.9%至31.3%,B1为0至28.3%,Ki67为3.5%至54.5%。以中位数LI作为“临界点”(细胞周期蛋白为12%;Ki67为22%),Kaplan-Meier生存分析显示,OPL的LI超过中位数的患者疾病进一步进展的风险显著增加(细胞周期蛋白A p=0.02,细胞周期蛋白B1 p=0.01,Ki67 p=0.025)。通过对细胞周期蛋白A和B1的LI进行联合分析,差异的显著性增加(p<0.01)。细胞周期分析对于识别OPL治疗后有疾病进一步进展风险的患者是有效的。需要进行多中心纵向试验来评估细胞周期标志物在其管理中的精确作用。