Relationship between chromosomal instability and intratumoral regional DNAploidy heterogeneity in primary gastric cancers

The purpose of this study was to elucidate the relationship between intratu moral regional heterogeneity in DNA ploidy and chromosomal instability (CIN ) in primary gastric adenocarcinomas. In 45 sporadic gastric adenocarcinoma s, we measured DNA ploidy and numerical aberrations for chromosomes 7, 11, 17, and 18 by laser scanning cytometry and fluorescence in situ hybridizati on, respectively, in small tissue specimens taken from 2 to 6 (on the avera ge 4) different portions of the same tumor. A total of 231 specimens includ ing 45 normal control specimens were examined. All 98 tumor specimens with DNA aneuploidy (DNA index greater than or equal to 1.2) showed large interc ellular variations in chromosome copy number, indicating CIN, In contrast, 85 tumor specimens with (near) diploidy (1.0 less than or equal to DNA inde x <1.2) exhibited much small intercellular variations in chromosome copy nu mber as compared with aneuploid specimens (P < 0.0001). The relationship be tween DNA ploidy and intercellular variation in chromosome copy number was true for tumors consisting of a mixture of (near) diploid and aneuploid sub populations. These data indicate that DNA aneuploidy is associated with CIN but that (near) diploidy is not. Intratumoral regional DNA ploidy heteroge neity was conspicuous in 33 (92%) of 36 tumors with regions of DNA aneuploi dy, and all aneuploid specimens showed great intercellular variation in chr omosome copy number, Diploid regions were predominant in early stage cancer s (intramucosal and submucosal cancers), and five of eight early cancers co ntained only diploid population. In contrast, all tumors without (near) dip loid regions were advanced cancers. These observations suggest that CIN is a necessary prerequisite for developing intratumoral DNA ploidy heterogenei ty with DNA aneuploidy.