Interrelationship between TP53gene deletion, protein expression and chromosome 17 aneusomy in gastric adenocarcinoma

Abstract

BackgroundThis study evaluates the existence of numerical alterations of chromosome 17 and TP53 gene deletion in gastric adenocarcinoma. The p53 protein expression was also evaluated, as well as, possible associations with clinicopathological characteristics.MethodsDual-color fluorescence in situ hybridization and immunostaining were performed in twenty gastric cancer samples of individuals from Northern Brazil.ResultsDeletion of TP53 was found in all samples. TP53 was inactivated mainly by single allelic deletion, varying to 7–39% of cells/case. Aneusomy of chromosome 17 was observed in 85% of cases. Chromosome 17 monosomy and gain were both observed in about half of cases. Cells with gain of chromosome 17 frequently presented TP53 deletion. The frequency of cells with two chr17 and one TP53 signals observed was higher in diffuse than in intestinal-type GC. Immunoreactivity of p53 was found only in intestinal-type samples. The frequency of cells with two chr17 and two TP53 signals found was higher in samples with positive p53 expression than in negative cases in intestinal-type GC.ConclusionWe suggest that TP53 deletion and chromosome 17 aneusomy is a common event in GC and other TP53 alterations, as mutation, may be implicated in the distinct carcinogenesis process of diffuse and intestinal types.

MYC, TP53, and Chromosome 17 Copy‐Number Alterations in Multiple Gastric Cancer Cell Lines and in Their Parental Primary Tumors

“…This finding corroborates our previous study using dual-color FISH for chr17/ TP53 in primary tumor samples, in which we observed that the frequency of cells with two chr17 and one TP53 signals was higher in the diffuse-type than in the intestinal-type GC [27]. …”

“…Although primary tumors of individuals from Northern Brazil present clonal crh17 trisomy or monosomy by FISH analysis [27], chr17 aneusomy is not the most frequent alteration within primary tumors of our population [7, 22, 28]. …”

Insulin-like growth factor binding protein-3 gene methylation and protein expression in gastric adenocarcinoma

“…It was also suggested that the loss of p53 expression leads to the suppression of IGFBP-3 in tumor cells [23]. In our population, we previously described that all gastric samples presented TP53 allelic deletions [24]. Thus, the feedback between p53 and IGFBP-3 may be lost in these samples and other pathways may be inducing IGFBP-3 expression.…”

“…We previously observed that only intestinal type gastric cancer samples presented p53 immunoreactivity [24]. Increased immunostaining of p53 can depend on either increased synthesis of wildtype protein or accumulation of mutated protein in the cell [25], which explains the significant difference in IGFBP-3 staining between intestinal (92.3%) and in diffuse type (67.9%).…”

hTERT, MYC and TP53 deregulation in gastric preneoplastic lesions

“…Previously we also reported the presence of p53 immunoreactivity in all intestinal-type gastric cancer of individuals from Northern Brazil [12]. The p53 immunoreactivity usually depends on the accumulation of mutated p53 proteins in the cell, which leads to a longer half-life [36].…”