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p53 表达状态与接受奥沙利铂为基础的辅助化疗的 III 期和高危 II 期结直肠癌患者的癌症特异性生存相关。

p53 expression status is associated with cancer-specific survival in stage III and high-risk stage II colorectal cancer patients treated with oxaliplatin-based adjuvant chemotherapy.

机构信息

Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea.

Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.

出版信息

Br J Cancer. 2019 Apr;120(8):797-805. doi: 10.1038/s41416-019-0429-2. Epub 2019 Mar 21.

Abstract

BACKGROUND

We attempted to elucidate whether p53 expression or TP53 mutation status was associated with cancer-specific survival in adjuvant FOLFOX-treated patients with stage III or high-risk stage II colorectal cancer (CRC).

METHODS

We analysed CRCs (N = 621) for the presence of TP53 alterations and for p53 expression, using targeted resequencing and immunohistochemistry. CRCs were grouped into four subsets according to the p53 expression status, which included p53-no, mild, moderate and strong expression.

RESULTS

The distributions of CRCs were 19.85, 11.05, 17.7% and 51.5% in the p53-no, mild, moderate and strong expression groups, respectively. Cases in the p53-mild to moderate expression group were associated with a more frequent proximal location, undifferentiated histology, lower N category, extraglandular mucin production, microsatellite instability, CIMP-P1, CK7 expression and decreased CDX2 expression compared with those of cases of the p53-no expression and p53-strong expression groups. According to survival analysis, the p53-mild expression group showed a poor 5-year relapse-free survival (hazard ratio (HR): 2.71, 95% confidence interval (CI) = 1.60-4.60, P < 0.001) and poor 5-year cancer-specific survival (HR: 2.90, 95% CI = 1.28-6.57, P = 0.011).

CONCLUSIONS

p53-mild expression status was found to be an independent prognostic marker in adjuvant FOLFOX-treated patients with stage III and high-risk stage II CRC.

摘要

背景

我们试图阐明 p53 表达或 TP53 突变状态是否与接受辅助 FOLFOX 治疗的 III 期或高危 II 期结直肠癌(CRC)患者的癌症特异性生存相关。

方法

我们使用靶向重测序和免疫组织化学分析了 621 例 CRC 中是否存在 TP53 改变和 p53 表达。CRC 根据 p53 表达状态分为四组,包括 p53-无、轻度、中度和强表达。

结果

p53-无、轻度、中度和强表达组的 CRC 分布分别为 19.85%、11.05%、17.7%和 51.5%。p53-轻度至中度表达组的病例更常位于近端、未分化组织学、较低的 N 分期、细胞外粘液产生、微卫星不稳定、CIMP-P1、CK7 表达和 CDX2 表达降低,与 p53-无表达和 p53-强表达组的病例相比。根据生存分析,p53-轻度表达组的 5 年无复发生存率(危险比(HR):2.71,95%置信区间(CI)=1.60-4.60,P<0.001)和 5 年癌症特异性生存率(HR:2.90,95%CI=1.28-6.57,P=0.011)较差。

结论

p53-轻度表达状态被发现是接受辅助 FOLFOX 治疗的 III 期和高危 II 期 CRC 患者的独立预后标志物。

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