Genetic mutations of p53 and k-ras in gastric carcinoma patients from Hunan, China

Chen, Han Chun; Chen, Hui Juan; Rao, Zhou Zhou; Wan, Xin; Tan, Bo; Zhang, Dian Zheng

doi:10.1007/s13277-010-0129-2

Cited by 11 publications

(6 citation statements)

References 25 publications

(29 reference statements)

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“…Although KRAS mutations represent a prognostic factor for colorectal and lung cancer, their correlation with the biological behaviour of gastric tumours is still poorly defined [38]–[40].…”

Section: Discussionmentioning

confidence: 99%

EGFR, HER-2 and KRAS in Canine Gastric Epithelial Tumors: A Potential Human Model?

et al. 2014

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Epidermal growth factor receptor (EGFR or HER-1) and its analog c-erbB-2 (HER-2) are protein tyrosine kinases correlated with prognosis and response to therapy in a variety of human cancers. KRAS mediates the transduction of signals between EGFR and the nucleus, and its mutation has been identified as a predictor of resistance to anti-EGFR drugs. In human oncology, the importance of the EGFR/HER-2/KRAS signalling pathway in gastric cancer is well established, and HER-2 testing is required before initiating therapy. Conversely, this pathway has never been investigated in canine gastric tumours. A total of 19 canine gastric epithelial neoplasms (5 adenomas and 14 carcinomas) were retrospectively evaluated for EGFR/HER-2 immunohistochemical expression and KRAS mutational status. Five (35.7%) carcinomas were classified as intestinal-type and 9 (64.3%) as diffuse-type. EGFR was overexpressed (≥1+) in 8 (42.1%) cases and HER-2 (3+) in 11 (57.9%) cases, regardless of tumour location or biological behaviour. The percentage of EGFR-positive tumours was significantly higher in the intestinal-type (80%) than in the diffuse-type (11.1%, p = 0.023). KRAS gene was wild type in 18 cases, whereas one mucinous carcinoma harboured a point mutation at codon 12 (G12R). EGFR and HER-2 may be promising prognostic and therapeutic targets in canine gastric epithelial neoplasms. The potential presence of KRAS mutation should be taken into account as a possible mechanism of drug resistance. Further studies are necessary to evaluate the role of dog as a model for human gastric cancer.

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Section: Discussionmentioning

confidence: 99%

EGFR, HER-2 and KRAS in Canine Gastric Epithelial Tumors: A Potential Human Model?

et al. 2014

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“…Similar to the current results, Chen et al reported that p53 mutation was associated with the initiation stages of gastric cancer. 27 Although the exact mechanism remains unclear, the presence of clonal EBV in every tumor cell suggests that EBV infection precedes the final transforming event giving rise to a tumor. 28 Yet, despite the association between advanced stage and p53 overexpression in EBVaGC tissue, no prognostic significance of p53 for DFS and OS was demonstrated.…”

Section: Discussionmentioning

confidence: 99%

Clinical Significance of p53 Protein Expression, Beta-catenin Expression and HER2 Expression for Epstein-Barr Virus-associated Gastric Cancer

et al. 2017

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This study assessed the expression of the p53 protein, beta-catenin, and HER2 and their prognostic implications in patients with EBV-associated gastric cancer (EBVaGC). After reviewing 1318 consecutive cases of surgically resected or endoscopic submucosal dissected gastric cancers, 117 patients were identified as EBV-positive using EBV-encoded RNA in-situ hybridization. The immunohistochemistry results were interpreted as follows: strong p53 nuclear expression in at least 50% of tumor nuclei was interpreted as a positive result, strong beta-catenin expression in at least 10% of cytoplasmic nuclei was interpreted as a positive result, and moderate or strong complete or basolateral membrane staining in 10% of tumor cells was interpreted as a positive result for HER2. Immunohistochemical staining for p53 was performed on tumor tissue from 105 patients, among whom 25 (23.8%) tested positive. Meanwhile, beta-catenin expression was positive in 10 patients (17.5%) and HER2 expression was positive in 8 patients (6.8%). The positive expression of p53 was significantly associated with a high T stage (p=0.006). More patients with lymph node metastasis were p53-positive (p=0.013). In the univariate analysis, the p53-positive patients showed significantly decreased disease-free survival (DFS) when compared with the p53-negative patients (p=0.022), although the p53 status was only marginally associated with overall survival (OS) (p=0.080). However, p53 expression showed no prognostic significance on DFS in the multivariate analysis. Moreover, beta-catenin and HER2 showed no association with DFS and OS in the survival analysis. The current study found a significant correlation between p53 expression and tumor progression and lymph node metastases in patients with EBVaGC.

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“…Similarly, in Chinese population, Chen et al [55] reported TP53 mutations in GC occurring in four exons affecting codons 131, 132, 133, 135, 149, 151, 162, 167, 173, 174, and 175 of exon 5, codons 193, 197, 213, and 215 of exon 6, codons 245, 246, 248, 249, and 270 of exon 7, and codons 271, 272, 273, and 282 of exon 8. Among the mutations, G:C to A:T transitions was the highest (41.7%), followed by A:T to G:C (25%), G:C to C:G (11.1%), G:C to T:A (8.3%), A:T to T:A (2.8%), and frameshift mutation.…”

Section: Mutations Of Tp53 Gene In Esophageal and Gastric Carcinogmentioning

confidence: 99%

Alterations of theTP53Gene in Gastric and Esophageal Carcinogenesis

Bellini

Cadamuro

Succi

et al. 2012

Journal of Biomedicine and Biotechnology

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TP53 genes is one of more important tumor suppressor gene, which acts as a potent transcription factor with fundamental role in the maintenance of genetic stability. The development of esophageal and gastric cancers is a multistep process resulting in successive accumulation of genetic alterations that culminates in the malignant transformation. Thus, this study highlights the participation of the main genetic alterations of the TP53 gene in esophageal and gastric carcinogenesis. Among these changes, high frequency of TP53 mutations, loss of heterozygosity (LOH), overexpression of the p53 protein, and consequently loss of p53 function, which would be early events in esophageal and gastric cancers, as well as an important biomarker of the prognosis and treatment response. Furthermore, Single Nucleotide Polymorphisms (SNPs) of TP53 have been implicated in the development and prognosis of several cancers, mainly TP53 codon 72 polymorphism whose role has been extensively studied in relation to susceptibility for esophageal and gastric cancer development.

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Genetic mutations of p53 and k-ras in gastric carcinoma patients from Hunan, China

Cited by 11 publications

References 25 publications

EGFR, HER-2 and KRAS in Canine Gastric Epithelial Tumors: A Potential Human Model?

EGFR, HER-2 and KRAS in Canine Gastric Epithelial Tumors: A Potential Human Model?

Clinical Significance of p53 Protein Expression, Beta-catenin Expression and HER2 Expression for Epstein-Barr Virus-associated Gastric Cancer

Alterations of theTP53Gene in Gastric and Esophageal Carcinogenesis

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