The Complete Loss of p53 Expression Uniquely Predicts Worse Prognosis in Colorectal Cancer.
The Complete Loss of p53 Expression Uniquely Predicts Worse Prognosis in Colorectal Cancer.
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p53表达完全缺失独特地预示着结直肠癌预后更差。
DOI：
10.3390/ijms23063252
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发表时间：
2022-03-17
影响因子：
5.6
通讯作者：
Inaguma S
中科院分区：
文献类型：
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作者：
Nagao K;Koshino A;Sugimura-Nagata A;Nagano A;Komura M;Ueki A;Ebi M;Ogasawara N;Tsuzuki T;Kasai K;Takahashi S;Kasugai K;Inaguma S
p53免疫组织化学被认为是反映潜在TP53突变状态的准确替代标记物，并在肿瘤诊断中具有实用性。在本研究中，我们对269例原发性CRCs进行了p53表达的免疫组化评价，以评估其在诊断病理学和诊断中的实用性。59例（23%）p53为野生型，143例（55%）p53过表达，50例（19%）p53完全缺失，10例（4%）为胞浆型。p53免疫反应性与肿瘤大小（p = 0.0056）、粘液产生（p = 0.0015）和错配修复（MMR）系统状态（p <0.0001）相关。此外，在野生型p53表达的CRC中，CDX2降低的病例数显著高于p53过表达（p = 0.012）或p53完全缺失（p = 0.043）的病例数。相反，在p53过表达的CRC中，ALCAM阳性病例明显少于p53野生型病例（p = 0.0045）。然而，p53免疫反应性与CDX2下调和ALCAM阳性定义的"干细胞样"免疫表型之间没有显著相关性。多变量考克斯风险回归分析确定了肾小管形成组织学（风险比[HR]= 0.17，p <0.0001）、年轻年龄（HR = 0.52，p = 0.021）和女性性别（HR = 0.55，p = 0.046）为潜在有利因素。分析还显示p53完全丢失（HR = 2.16，p = 0.0087）、不完全切除（HR = 2.65，p = 0.0068）和腹膜转移（HR = 5.32，p <0.0001）是CRC患者的潜在独立风险因素。根据术后化疗分类的亚队列生存分析显示，野生型p53表达的CRC患者往往比化疗后过度表达或完全丧失的患者生存率更高。因此，p53免疫组化可用于结直肠癌的诊断和化疗靶点的选择。
p53 immunohistochemistry is considered an accurate surrogate marker reflecting the underlying TP53 mutation status and has utility in tumor diagnostics. In the present study, 269 primary CRCs were immunohistochemically evaluated for p53 expression to assess its utility in diagnostic pathology and prognostication. p53 expression was wild-type in 59 cases (23%), overexpressed in 143 cases (55%), completely lost in 50 cases (19%), and cytoplasmic in 10 cases (4%). p53 immunoreactivity was associated with tumor size (p = 0.0056), mucus production (p = 0.0015), and mismatch repair (MMR) system status (p < 0.0001). Furthermore, among CRCs with wild-type p53 expression, a significantly higher number of cases had decreased CDX2 than those with p53 overexpression (p = 0.012) or complete p53 loss (p = 0.043). In contrast, among CRCs with p53 overexpression, there were significantly fewer ALCAM-positive cases than p53 wild-type cases (p = 0.0045). However, no significant association was detected between p53 immunoreactivity and the “stem-like” immunophenotype defined by CDX2 downregulation and ALCAM-positivity. Multivariate Cox hazards regression analysis identified tubular-forming histology (hazard ratio [HR] = 0.17, p < 0.0001), younger age (HR = 0.52, p = 0.021), and female sex (HR = 0.55, p = 0.046) as potential favorable factors. The analysis also revealed complete p53 loss (HR = 2.16, p = 0.0087), incomplete resection (HR = 2.65, p = 0.0068), and peritoneal metastasis (HR = 5.32, p < 0.0001) as potential independent risk factors for patients with CRC. The sub-cohort survival analyses classified according to chemotherapy after surgery revealed that CRC patients with wild-type p53 expression tended to have better survival than those with overexpression or complete loss after chemotherapy. Thus, immunohistochemistry for p53 could be used for the prognostication and chemotherapy target selection of patients with CRC.
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影响因子：
11.2
作者：
Huang EH;Hynes MJ;Zhang T;Ginestier C;Dontu G;Appelman H;Fields JZ;Wicha MS;Boman BM
通讯作者：
Boman BM
影响因子：
9.8
作者：
Jain AK;Allton K;Iacovino M;Mahen E;Milczarek RJ;Zwaka TP;Kyba M;Barton MC
通讯作者：
Barton MC
对医疗统计信息的自由使用的易于使用的软件“ EZR”的调查。
影响因子：
4.8
作者：
Kanda Y
通讯作者：
Kanda Y
DOI：
10.1038/modpathol.2016.185
发表时间：
2017-03
期刊：
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
影响因子：
--
作者：
Inaguma S;Lasota J;Wang Z;Felisiak-Golabek A;Ikeda H;Miettinen M
通讯作者：
Miettinen M
影响因子：
29.4
作者：
Levin TG;Powell AE;Davies PS;Silk AD;Dismuke AD;Anderson EC;Swain JR;Wong MH
通讯作者：
Wong MH