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p53 Immunohistochemistry Patterns Are Surrogate Biomarkers for TP53 Mutations in Gastrointestinal Neuroendocrine Neoplasms

文献类型：期刊论文

作者Li, Junjie5; Wang, Jing5; Su, Dan4; Nie, Xiu3; Liu, Yueping2; Teng, Lianghong1; Pang, Junyi5; Wu, Huanwen5; Liang, Zhiyong5
刊名GASTROENTEROLOGY RESEARCH AND PRACTICE
出版日期2021-12-15
卷号2021
ISSN号1687-6121
DOI10.1155/2021/2510195
通讯作者Wu, Huanwen(whw14093@163.com) ; Liang, Zhiyong(liangzhiyong1220@yahoo.com)
英文摘要Aims. The aim of this study was to establish p53 immunohistochemistry (IHC) patterns to predict TP53 mutations in gastrointestinal neuroendocrine neoplasms (GI-NENs) and to determine whether p53 IHC patterns could be used for the differential diagnosis of neuroendocrine neoplasms. Methods. TP53 gene sequencing and p53 IHC were performed on formalin-fixed paraffin-embedded (FFPE) tissue samples from 92 patients diagnosed with GI-NENs from five medical centers. Results. The cohort included 35 well-differentiated neuroendocrine tumors and 57 poorly differentiated neuroendocrine carcinomas. Gene sequencing revealed 38 wild-type TP53 and 54 TP53 mutations. p53 expression was interpreted as follows: pattern A, p53 was absent from all tumor cells; pattern B, scattered and weak p53 expression in 1-20% of tumor cells; and pattern C was subclassified as pattern C1: variable p53 staining intensity in 21-60% of tumor cells and tumor cell nests with focal strong positive p53 staining and pattern C2: strong p53 staining in more than 60% of tumor cells. p53 IHC patterns were evaluated as a binary classifier where pattern B predicted wild-type TP53, and patterns A and C predicted TP53 mutations. The sensitivity, specificity, and overall accuracy of this binary classification to predict TP53 status were 0.963, 0.868, and 0.924, respectively. p53 IHC patterns were also correlated with TP53 mutation types. Most cases with pattern A harboured loss-of-function (LOF) mutations, whereas patterns B and C tended to indicate wild-type TP53 and gain-of-function (GOF) mutations, respectively. Furthermore, most of the well-differentiated NETs showed pattern B, whereas pattern C2 was more common in poorly differentiated NECs. Finally, staining interpretation between different observers also yielded high reproducibility. Conclusions. p53 IHC patterns may be used as predictors of TP53 gene mutations and therefore could be potential surrogate markers for TP53 mutations in GI-NENs and could distinguish between well-differentiated NETs and poorly differentiated NECs.
WOS关键词MUTANT P53 ; CANCER ; EXPRESSION ; CARCINOMA ; TUMORS ; GAIN
资助项目Chinese Academy of Medical Sciences (CAMS) Innovation Funds for Medical Sciences[2016-I2M-1-002] ; Chinese Academy of Medical Sciences (CAMS) Innovation Funds for Medical Sciences[2017-I2M-1-001]
WOS研究方向Gastroenterology & Hepatology
语种英语
WOS记录号WOS:000737186100001
出版者HINDAWI LTD
资助机构Chinese Academy of Medical Sciences (CAMS) Innovation Funds for Medical Sciences
源URL[http://ir.hfcas.ac.cn:8080/handle/334002/127201]  
专题中国科学院合肥物质科学研究院
通讯作者Wu, Huanwen; Liang, Zhiyong
作者单位1.Capital Med Univ, Xuanwu Hosp, Dept Pathol, Beijing 100053, Peoples R China
2.Hebei Med Univ, Hosp 4, Hebei Canc Hosp, Dept Pathol, Shijiazhuang 050011, Hebei, Peoples R China
3.Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Pathol, Wuhan 430022, Hubei, Peoples R China
4.Univ Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp, Dept Pathol, Hangzhou 310022, Zhejiang, Peoples R China
5.Chinese Acad Med Sci & Peking Union Med Coll, Peking Union Med Coll Hosp, Mol Pathol Res Ctr, Dept Pathol,State Key Lab Complex Severe & Rare D, Beijing 100730, Peoples R China
推荐引用方式
GB/T 7714		 Li, Junjie,Wang, Jing,Su, Dan,et al. p53 Immunohistochemistry Patterns Are Surrogate Biomarkers for TP53 Mutations in Gastrointestinal Neuroendocrine Neoplasms[J]. GASTROENTEROLOGY RESEARCH AND PRACTICE,2021,2021.
APA Li, Junjie.,Wang, Jing.,Su, Dan.,Nie, Xiu.,Liu, Yueping.,...&Liang, Zhiyong.(2021).p53 Immunohistochemistry Patterns Are Surrogate Biomarkers for TP53 Mutations in Gastrointestinal Neuroendocrine Neoplasms.GASTROENTEROLOGY RESEARCH AND PRACTICE,2021.
MLA Li, Junjie,et al."p53 Immunohistochemistry Patterns Are Surrogate Biomarkers for TP53 Mutations in Gastrointestinal Neuroendocrine Neoplasms".GASTROENTEROLOGY RESEARCH AND PRACTICE 2021(2021).

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来源：合肥物质科学研究院

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