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

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机构： [1]Department of Pathology, State Key Laboratory of Complex Severe and Rare Diseases, Molecular Pathology Research Center,Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College,Beijing 100730, China [2]Department of Pathology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital),Hangzhou, 310022 Zhejiang, China [3]Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan,430022 Hubei, China [4]Department of Pathology, The Fourth Hospital of Hebei Medical University/Hebei Cancer Hospital, Shijiazhuang,050011 Hebei, China [5]Department of Pathology, Xuanwu Hospital Capital Medical University, Beijing 100053, China

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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.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.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.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.Copyright © 2021 Junjie Li et al.

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出版当年[2021]版：

大类 | 4 区医学

小类 | 4 区胃肠肝病学

最新[2025]版：

大类 | 4 区医学

小类 | 4 区胃肠肝病学

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出版当年[2021]版：

Q4 GASTROENTEROLOGY & HEPATOLOGY

最新[2024]版：

Q4 GASTROENTEROLOGY & HEPATOLOGY

影响因子： 1.4 最新[2024版] 1.9 最新五年平均 1.919 出版当年[2021版] 2.439 出版当年五年平均 2.26 出版前一年[2020版] 2 出版后一年[2022版]

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第一作者机构： [1]Department of Pathology, State Key Laboratory of Complex Severe and Rare Diseases, Molecular Pathology Research Center,Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College,Beijing 100730, China

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