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

doi:10.1155/2021/2510195

	p53 Immunohistochemistry Patterns Are Surrogate Biomarkers for TP53 Mutations in Gastrointestinal Neuroendocrine Neoplasms
	Li, Junjie 2; Wang, Jing 2; Su, Dan 3; Nie, Xiu 4; Liu, Yueping 1; Teng, Lianghong 5; Pang, Junyi 2; Wu, Huanwen 2; Liang, Zhiyong 2
刊名	GASTROENTEROLOGY RESEARCH AND PRACTICE
	2021-12-15
卷号	2021
ISSN号	1687-6121
DOI	10.1155/2021/2510195
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.
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关键词	MUTANT P53 ; CANCER ; EXPRESSION ; CARCINOMA ; TUMORS ; GAIN
WOS研究方向	Gastroenterology & Hepatology
语种	英语
出版者	HINDAWI LTD
WOS记录号	WOS:000737186100001
资助机构	Chinese Academy of Medical Sciences (CAMS) Innovation Funds for Medical Sciences
内容类型	期刊论文
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.Hebei Med Univ, Hosp 4, Hebei Canc Hosp, Dept Pathol, Shijiazhuang 050011, Hebei, Peoples R China 2.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 3.Univ Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp, Dept Pathol, Hangzhou 310022, Zhejiang, Peoples R China 4.Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Pathol, Wuhan 430022, Hubei, Peoples R China 5.Capital Med Univ, Xuanwu Hosp, Dept Pathol, Beijing 100053, 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).