Bourhis J, Le M G, Barrois M, Gerbaulet A, Jeannel D, Duvillard P, Le Doussal V, Chassagne D, Riou G
Département de Statistiques, INSERM U 287, Institut Gustave Roussy, Villejuif, France.
J Clin Oncol. 1990 Nov;8(11):1789-96. doi: 10.1200/JCO.1990.8.11.1789.
The prognostic effect of c-myc oncogene overexpression was assessed in a multivariate analysis of 93 patients with invasive carcinoma of the cervix, stage Ib, IIa, and IIb proximal. The treatment was based on the association of brachytherapy-colpohysterectomy and lymphadenectomy. Analysis of c-myc gene expression was done using Northern and slot blot hybridization techniques. Overexpression of c-myc (ie, levels at least three times the mean observed in normal tissues) was present in 33% of the tumors. The proportion of carcinomas with c-myc overexpression significantly increased with the size of the primary tumor (P = .04). No relationship was found between c-myc overexpression and the other clinical and histologic parameters, including the nodal status. The relative risk of relapse (overall, pelvic failure, distant metastases) was analyzed in a Cox's proportional hazards model. Three factors were significantly related to the risk of overall relapse when the multivariate analysis was performed, namely, the tumor size, the nodal status, and c-myc expression. A combination of c-myc expression and the nodal status provided a very accurate indication of the risk of relapse. Indeed, patients with negative nodes had a 3-year disease-free survival rate of 93% (95% confidence interval [Cl], 79% to 98%) when c-myc was expressed at a normal level, whereas this rate was only 51% (95% Cl, 26% to 63%) when c-myc was overexpressed (log-rank test, P = .02). In addition, in the subgroup of patients with positive nodes, this rate was 44% (95% Cl, 25% to 77%) and 15% (95% Cl, 4% to 49%) when c-myc gene was expressed at normal level, or overexpressed, respectively. Finally, c-myc gene overexpression was, in the multivariate analysis, the first factor selected by the model regarding the risk of distant metastases.
在一项对93例Ib期、IIa期和近端IIb期宫颈浸润癌患者的多因素分析中，评估了c-myc癌基因过表达的预后影响。治疗方案基于近距离放射治疗-阴道子宫切除术和淋巴结清扫术的联合应用。使用Northern和狭缝印迹杂交技术对c-myc基因表达进行分析。33%的肿瘤存在c-myc过表达（即水平至少为正常组织中观察到的平均值的三倍）。c-myc过表达的癌的比例随原发肿瘤大小显著增加（P = 0.04）。未发现c-myc过表达与其他临床和组织学参数之间存在关联，包括淋巴结状态。在Cox比例风险模型中分析复发的相对风险（总体、盆腔失败、远处转移）。进行多因素分析时，三个因素与总体复发风险显著相关，即肿瘤大小、淋巴结状态和c-myc表达。c-myc表达和淋巴结状态的组合能非常准确地指示复发风险。实际上，当c-myc以正常水平表达时，淋巴结阴性的患者3年无病生存率为93%（95%置信区间[Cl]，79%至98%），而当c-myc过表达时，该率仅为51%（95% Cl，26%至63%）（对数秩检验，P = 0.02）。此外，在淋巴结阳性的患者亚组中，当c-myc基因以正常水平表达或过表达时，该率分别为44%（95% Cl，25%至77%）和15%（95% Cl，4%至49%）。最后，在多因素分析中，c-myc基因过表达是模型选择的关于远处转移风险的首要因素。
