Bouzourene H, Gervaz P, Cerottini J P, Benhattar J, Chaubert P, Saraga E, Pampallona S, Bosman F T, Givel J C
Institute of Pathology, Lausanne, Switzerland.
Eur J Cancer. 2000 May;36(8):1008-15. doi: 10.1016/s0959-8049(00)00036-8.
Mutations of the TP53 and Ki-ras genes have been reported to be of prognostic importance in colorectal carcinomas. An increased intracellular concentration of the p53 protein, although not identical to, is sometimes seen in tumours with TP53 mutation and has been correlated with poor prognosis in some tumour types. Previous colorectal cancer studies, addressing the prognostic importance of Ki-ras mutation and TP53 aberrations, yielded contradictory results. The aim of this study was to determine in a clinically and therapeutically homogeneous group of 122 sporadic Dukes' B colorectal carcinomas with a median follow-up of 67 months (3-144 months) whether or not p53 protein expression, TP53 mutation and K-ras mutation correlated with prognosis. p53 staining was performed by immunohistochemistry, using the monoclonal antibody DO7 on paraffin-embedded tissue. Mutations in exons 5-8 of the TP53 gene and in codons 12 and 13 of the K-ras gene were assayed in paraffin-embedded tissue by the single-strand conformation polymorphism (SSCP) assay. Nuclear p53 staining was found in 57 (47%) tumours. Aberrant migration patterns indicating mutation of the TP53 gene were found in 39 (32%) tumours. Forty-six carcinomas (38%) showed a mutation of the Ki-ras codons 12 or 13. In a univariate analysis, patients with wild-type TP53 status showed a trend towards better survival, compared with those with mutated TP53 (log-rank test, P = 0.051). Likewise, tumours immunohistochemically positive for p53 showed a worse prognosis than p53-negative tumours (P = 0.010). The presence or absence of mutations in Ki-ras did not correlate with prognosis (P = 0.703). In multivariate analysis, only p53 immunoreactivity emerged as an independent marker for prognosis hazard ratio (HR) = 2.16, 95% confidence interval (CI) 1.12-4.11, P = 0.02). Assessment of p53 protein expression is more discriminative than TP53 mutation to predict the outcome of Dukes' stage B tumours and could be a useful tool to identify patients who might benefit from adjuvant therapy.
据报道，TP53和Ki-ras基因的突变在结直肠癌中具有预后意义。p53蛋白细胞内浓度升高，虽然与之不同，但有时在发生TP53突变的肿瘤中可见，并且在某些肿瘤类型中与预后不良相关。以往关于Ki-ras突变和TP53异常的预后意义的结直肠癌研究结果相互矛盾。本研究的目的是在一组临床和治疗上均一的122例散发性Dukes B期结直肠癌患者中确定p53蛋白表达、TP53突变和K-ras突变是否与预后相关，这些患者的中位随访时间为67个月（3 - 144个月）。使用单克隆抗体DO7对石蜡包埋组织进行免疫组织化学染色以检测p53。通过单链构象多态性（SSCP）分析检测石蜡包埋组织中TP53基因第5 - 8外显子以及K-ras基因第12和13密码子的突变。在57例（47%）肿瘤中发现细胞核p53染色。在39例（32%）肿瘤中发现表明TP53基因突变的异常迁移模式。46例癌（38%）显示Ki-ras第12或13密码子突变。在单因素分析中，与TP53突变的患者相比，TP53野生型状态的患者有生存更好的趋势（对数秩检验，P = 0.051）。同样，p53免疫组化阳性的肿瘤比阴性肿瘤预后更差（P = 0.010）。Ki-ras突变的有无与预后无关（P = 0.703）。在多因素分析中，只有p53免疫反应性作为预后的独立标志物出现（风险比[HR] = 2.16，95%置信区间[CI] 1.12 - 4.11，P = 0.02）。评估p53蛋白表达在预测Dukes B期肿瘤的结局方面比TP53突变更具鉴别力，并且可能是识别可能从辅助治疗中获益的患者的有用工具。
