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结直肠癌中的DCC蛋白与预后

The DCC protein and prognosis in colorectal cancer.

作者信息

Shibata D, Reale M A, Lavin P, Silverman M, Fearon E R, Steele G, Jessup J M, Loda M, Summerhayes I C

机构信息

Department of Surgery, New England Deaconess Hospital, Harvard Medical School, Boston, MA 02215, USA.

出版信息

N Engl J Med. 1996 Dec 5;335(23):1727-32. doi: 10.1056/NEJM199612053352303.

Abstract

BACKGROUND

Allelic loss of chromosome 18q predicts a poor outcome in patients with stage II colorectal cancer. Although the specific gene inactivated by this allelic loss has not been elucidated, the DCC (deleted in colorectal cancer) gene is a candidate. We investigated whether the expression of the DCC protein in tumor cells is a prognostic marker in colorectal carcinoma.

METHODS

The expression of DCC was evaluated immunohistochemically in 132 paraffin-embedded samples from patients with curatively resected stage II and III colorectal carcinomas. The Cox proportional-hazards model was used to adjust for covariates including age, sex, tumor site, degree of tumor differentiation, and use of adjuvant therapy.

RESULTS

The expression of DCC was a strong positive predictive factor for survival in both stage II and stage III colorectal carcinomas. In patients with stage II disease whose tumors expressed DCC, the five-year survival rate was 94.3 percent, whereas in patients with DCC-negative tumors, the survival rate was 61.6 percent (P<0.001). In patients with stage III disease, the respective survival rates were 59.3 percent and 33.2 percent (P=0.03).

CONCLUSIONS

DCC is a prognostic marker in patients with stage II or stage III colorectal cancer. In stage II colorectal carcinomas, the absence of DCC identifies a subgroup of patients with lesions that behave like stage III cancers. These findings may thus have therapeutic implications in this group of patients.

摘要

背景

18号染色体长臂等位基因缺失预示着II期结直肠癌患者预后不良。尽管尚未阐明因该等位基因缺失而失活的具体基因,但结直肠癌缺失基因(DCC)是一个候选基因。我们研究了肿瘤细胞中DCC蛋白的表达是否为结直肠癌的预后标志物。

方法

采用免疫组织化学方法评估132例接受根治性切除的II期和III期结直肠癌患者石蜡包埋样本中DCC的表达。使用Cox比例风险模型对年龄、性别、肿瘤部位、肿瘤分化程度和辅助治疗的使用等协变量进行校正。

结果

DCC的表达是II期和III期结直肠癌患者生存的强有力的阳性预测因子。在肿瘤表达DCC的II期疾病患者中,五年生存率为94.3%,而在DCC阴性肿瘤患者中,生存率为61.6%(P<0.001)。在III期疾病患者中,相应的生存率分别为59.3%和33.2%(P=0.03)。

结论

DCC是II期或III期结直肠癌患者的预后标志物。在II期结直肠癌中,DCC的缺失确定了一组具有类似III期癌症行为病变的患者亚组。因此,这些发现可能对该组患者具有治疗意义。

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