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