TP53 Co-Mutational Features and NGS-Calibrated Immunohistochemistry Threshold in Gastric Cancer

Yu, Ran; Sun, Tingyi; Zhang, Xianwei; Li, Zhen; Xu, Yang; Liu, Kaihua; Shi, Yuqian; Wu, Xue; Shao, Yang; Kong, Lingfei

doi:10.2147/ott.s321949

Cited by 3 publications

(1 citation statement)

References 37 publications

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“…It is known that the presence of a high tumor mutation burden (TMB-H) in PD-L1positive tumors is accompanied by defects in the DNA repair system [6,21]. This fact is consistent with our data, which showed a PD-L1-positive tumor status was characterized by heterogeneity and diversity of the mutation spectrum in the tumor.…”

Section: Genetic Markers In Gc Patients Depending On Her2 and Pd-l1 S...supporting

confidence: 92%

Targeted Sequencing in Gastric Cancer: Association with Tumor Molecular Characteristics and FLOT Therapy Effectiveness

Spirina,

Avgustinovich,

Bakina

et al. 2024

CIMB

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Heterogeneity of gastric cancer (GC) is the main trigger of the disease’s relapse. The aim of this study was to investigate the connections between targeted genes, cancer clinical features, and the effectiveness of FLOT chemotherapy. Twenty-one patients with gastric cancers (GCs) were included in this study. Tumor-targeted sequencing was conducted, and real-time PCR was used to assess the expression of molecular markers in tumors. Seven patients with stabilization had mutations that were related to their response to therapy and were relevant to the tumor phenotype. Two patients had two mutations. The number of patients with TP53 mutations increased in HER2-positive tumor status. PD-L1-positive cancers had mutations in KRAS, TP53, PIK3CA, PTEN, and ERBB, which resulted in an increase in PD-1 expression. TP53 mutation and PTEN mutation are associated with changes in factors associated with neoangiogenesis. In concusion, patients who did not have aggressive growth markers that were verified by molecular features had the best response to treatment, including complete morphologic regression.

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Section: Genetic Markers In Gc Patients Depending On Her2 and Pd-l1 S...supporting

confidence: 92%

Targeted Sequencing in Gastric Cancer: Association with Tumor Molecular Characteristics and FLOT Therapy Effectiveness

Spirina,

Avgustinovich,

Bakina

et al. 2024

CIMB

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The pattern-based interpretation of p53 immunohistochemical expression as a surrogate marker for TP53 mutations in colorectal cancer

Osakabe,

Yamada,

Sugimoto

et al. 2024

Virchows Arch

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Mutations in the TP53 gene, most commonly observed in colorectal cancer (CRC), play an essential role in colorectal carcinogenesis. Although p53 immunohistochemical (IHC) expression patterns have been argued to serve as an excellent surrogate marker for TP53 mutations, its performance has not been confirmed in CRC. We aimed to determine whether p53 IHC expression patterns accurately predict TP53 mutation status as examined by next-generation sequencing (NGS). We performed p53 IHC and sequencing of TP53 by NGS in 92 CRC cases with a microsatellite stable phenotype to investigate the correlation between TP53 mutation status and p53 IHC expression. The concordance between p53 IHC and TP53 mutation was 84/92 (91.3%) overall. However, 6 mutant cases were found in 39 cases with a wild-type IHC pattern. Additionally, there were two discordant cases in which an abnormal p53 IHC pattern (overexpression or cytoplasmic pattern) was found, while NGS detected wild-type p53. Therefore, the optimized p53 IHC performs well and serves as a surrogate test for TP53 mutation in CRC cases. Furthermore, it demonstrates excellent reproducibility between two independent experienced pathologists and may have novel clinical utility for molecular classification algorithms in CRC. We suggest that the four-tier classification of p53 IHC patterns is helpful to evaluate molecular colorectal carcinogenesis.

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TP53 in AML and MDS: The new (old) kid on the block

Marks¹,

Wang²,

Fenu³

et al. 2023

Blood Reviews

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TP53 Co-Mutational Features and NGS-Calibrated Immunohistochemistry Threshold in Gastric Cancer

Cited by 3 publications

References 37 publications

Targeted Sequencing in Gastric Cancer: Association with Tumor Molecular Characteristics and FLOT Therapy Effectiveness

Targeted Sequencing in Gastric Cancer: Association with Tumor Molecular Characteristics and FLOT Therapy Effectiveness

The pattern-based interpretation of p53 immunohistochemical expression as a surrogate marker for TP53 mutations in colorectal cancer

TP53 in AML and MDS: The new (old) kid on the block

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