DNA ploidy heterogeneity in early and advanced gastric cancers

To evaluate the clinical utility of flow cytometric DNA analysis in gastric cancers, four or more fresh tissue specimens were systematically taken from gastric cancers in 127 consecutive patients including 68 early cancers. DNA ploidy and its variation in individual tumors were determined, and the data were related to clinicopathologic findings. DNA aneuploidy was detected frequently (84.3%) irrespective of tumor progression and correlated significantly with histologic grade (G1-2 [89.6%] vs. G3-4 [76.0%], P < 0.05). DNA ploidy heterogeneity was found in 67.7% of tumors and correlated with invasion depth (mucosa [40.5%] vs. submucosa-serosa [81.2%], P < 0.001), regional lymph node metastases (negative [58.4%] vs. positive [82.0%], P < 0.01), and stage grouping (I [58.8%] vs. II-IV [86.0%], P < 0.01). The maximum DNA index of a tumor correlated significantly with invasion depth (mucosa [1.16, median] vs. submucosa [1.82], P < 0.01) and lymph node metastases (negative [1.22] vs. positive [1.86], P < 0.001). The DNA index of the subpopulation that was the most widely distributed within the tumor was significantly associated with lymph node metastases (negative [1.14, median] vs. positive [1.44], P < 0.001) and histologic grade (G1-2 [1.37] vs. G3-4 [1.12], P < 0.001). More than 80% of the diploid and/or single aneuploid stemline tumors were stage I, whereas more than half of diploid and multiple aneuploid stemline tumors were stage IV. Variation in DNA ploidy rather than presence of DNA aneuploidy correlates best with progression of gastric cancer.