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p53和p33(ING1b)在Dukes'C期结直肠癌患者中的预测价值。

The predictive value of p53 and p33(ING1b) in patients with Dukes'C colorectal cancer.

作者信息

Ahmed I A M, Kelly S B, Anderson J J, Angus B, Challen C, Lunec J

机构信息

Bishop Auckland General Hospital, Bishop Auckland, County Durham, UK.

出版信息

Colorectal Dis. 2008 May;10(4):344-51. doi: 10.1111/j.1463-1318.2007.01317.x. Epub 2007 Oct 19.

Abstract

OBJECTIVE

Identification of biological markers that may predict response to chemotherapy would allow the individualization of treatment by enabling selection of patients most likely to benefit from chemotherapy. The aims of this study were to determine whether p53 mutation status and p53 and p33(ING1b) protein expression can predict which patients with Dukes' C colorectal cancer following curative surgical resection respond to adjuvant chemotherapy with 5-fluorouracil (5-FU).

METHOD

Patients with Dukes'C colorectal cancer (n = 41) were studied. DNA was extracted and analysed for p53 mutation using PCR-based direct DNA sequencing. Tumours were analysed for p53 protein expression by immunohistochemistry using DO-7 monoclonal antibody and for p33(ING1b) protein expression using GN1 monoclonal antibody.

RESULTS

There was a significant association between p53 mutation status analysed by gene sequencing and overall and metastasis-free survival (P = 0.03 and 0.004, respectively, log-rank test). By contrast, no significant correlation was found between p53 and p33(ING1b) protein expression and overall or metastasis-free survival.

CONCLUSION

In patients with Dukes'C colorectal cancer who underwent curative surgical resection of the primary tumour, followed by 5-FU-based adjuvant chemotherapy, p53 mutation status as assessed by gene sequencing is a significant predictor of overall and metastasis-free survival.

摘要

目的

鉴定可能预测化疗反应的生物标志物,通过选择最有可能从化疗中获益的患者,实现治疗的个体化。本研究的目的是确定p53突变状态以及p53和p33(ING1b)蛋白表达能否预测哪些接受根治性手术切除的 Dukes' C 期结直肠癌患者对 5-氟尿嘧啶(5-FU)辅助化疗有反应。

方法

对41例 Dukes' C 期结直肠癌患者进行研究。提取DNA,采用基于PCR的直接DNA测序分析p53突变。使用DO-7单克隆抗体通过免疫组织化学分析肿瘤的p53蛋白表达,使用GN1单克隆抗体分析p33(ING1b)蛋白表达。

结果

通过基因测序分析的p53突变状态与总生存期和无转移生存期之间存在显著关联(对数秩检验,P分别为0.03和0.004)。相比之下,未发现p53和p33(ING1b)蛋白表达与总生存期或无转移生存期之间存在显著相关性。

结论

在接受原发性肿瘤根治性手术切除并随后进行基于5-FU的辅助化疗的 Dukes' C 期结直肠癌患者中,通过基因测序评估的p53突变状态是总生存期和无转移生存期的重要预测指标。

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