Abstract
This analysis of DNA‐ploidy heterogeneity in advanced gastric carcinomas is consistent with the hypothesis of the emergence of a single aneuploid cell clone as a crucial mechanism in the progression from early gastric carcinoma to advanced gastric cancer. The prognostic value of DNA‐ploidy in gastric cancers has been a matter of controversy. Tumour DNA‐ploidy heterogeneity, the presence within the same tumour of multiple stemlines differing in DNA content, has been described in various tumours including gastric cancers. The occurrence of such heterogeneity has been accepted as an explanation for the divergent DNA‐ploidy results in this type of tumours. A previous study of early gastric cancers suggested that in pure diploid superficial carcinomas, genetic instability might lead to a cell clone which has undergone a ploidy shift and is more aggressive. If so, this would initially result in DNA‐ploidy heterogeneity. Proliferative dominance of the aneuploid clone could eventually evolve to a homogeneous aneuploid tumour. In order to test this hypothesis, we studied DNA‐aneuploidy and DNA‐ploidy heterogeneity in advanced gastric carcinomas. We performed DNA cytophotometry on multiple samples collected from 16 advanced gastric carcinomas and found 15 DNA‐aneuploid tumours (94%) and one diploid tumour. Multiple DNA‐stemlines were found in 4 cases (26%). Analysis of proliferative activity performed on the same samples revealed higher proliferation rate in DNA‐ploidy homogeneous tumours than in aneuploid heterogeneous tumours. Heterogeneous tumours did not overexpress p53. These results confirm that DNA‐aneuploidy is frequent in advanced gastric cancer and demonstrate that a majority of these aneuploid tumours are not DNA‐ploidy heterogeneous. Furthermore, the higher proliferative activity in homogeneous‐aneuploid carcinomas and their more frequent overexpression of p53 support the hypothesis that in gastric cancer tumour progression implies the development of a dominant and more aggressive (higher proliferative activity, p53 overexpression) aneuploid cell clone.
Highlights
Several studies have reported a correlation between DNA-ploidy and prognosis in gastric carcinoma [1,11,12,13,26,29,34]
On the basis of these results we considered the possibility that in DNA-diploid early gastric carcinomas, instability of the genome leads to the emergence of aneuploid cell clones, reflected in DNA-ploidy heterogeneity
Antigen retrieval was performed and the sections were preincubated for 15 min in phosphate buffer saline (PBS) containing 5% albumin from bovine serum (BSA) and incubated with the relevant antibody at room temperature for 60 min, washed with PBS and subsequently incubated with the second biotinylated antibody at RT for 30 min
Summary
Several studies have reported a correlation between DNA-ploidy and prognosis in gastric carcinoma [1,11,12,13,26,29,34]. The presence of intratumoral heterogeneity in DNA-ploidy is generally accepted, and has been described in various tumours [2,3,6,7,10,14,17,18,19,20,21,22,23,24,30,31,33,34,35]. Some authors have indicated that DNA content heterogeneity is better correlated to tumour progression in gastric carcinomas than presence of aneuploidy [7,28]
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Schedule a callMore From: Cellular oncology : the official journal of the International Society for Cellular Oncology
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