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.

[Clinical significance of DNA ploidy heterogeneity in early gastric cancers].

To evaluate the clinical significance of DNA ploidy heterogeneity (DH), four or more fresh tissue specimens were obtained from a tumor in 68 resected early gastric cancers. DNA content was measured by flow cytometry and the presence of DH was prospectively investigated. The incidence of DH correlated to invasion depth (m < sm), lymph vessel invasion (negative < positive) and tumor size (10 mm or less in diameter < more than 10). When the criteria of indication for minimum surgery were determined as the intramucosal cancer without n, ly and v factor, 85% of contraindication cases demonstrated DH. These results indicate that DH is a useful marker of tumor progression in early gastric cancer and will be an aid for determining indications for minimum resection.

[Flow cytometric analysis of DNA ploidy in intramucosal gastric carcinoma].

In order to investigate whether or not DNA ploidy was altered in intramucosal gastric carcinomas, nuclear DNA content of biopsy specimen was measured using flow cytometry in 38 intramucosal carcinomas. DNA aneuploidy was detected in 27 of 38 lesions (71.1%), and noted more frequently in differentiated carcinomas than in undifferentiated ones (83.0% vs. 20.0%, p < 0.01). There was no significant relationship between the frequency of DNA aneuploidy and macroscopical type or tumor size. DNA aneuploidy was even found in two of three minute carcinomas (5 mm or less in diameter). DNA indices showed 1.2 or lower values in 40% of the lesions with DNA aneuploidy. The average value of DNA index was significantly larger in depressed type than in elevated type (p < 0.01). In conclusion, DNA ploidy is altered in most differentiated intramucosal carcinomas. A high resolution method is essential for accurate determination of DNA ploidy in intramucosal carcinomas, especially elevated ones.

[Flow cytometric DNA analysis of colorectal carcinoma in adenoma].

We evaluated the DNA ploidy in 23 lesions of colorectal carcinoma in adenoma (CIA) and 90 adenomas without carcinomas by flow cytometry using fresh samples. DNA ploidy of carcinoma and adenoma components were assessed, respectively, with 17 paraffin-embedded samples of CIAs. The incidence of DNA aneuploidy (AP) was significantly higher in CIAs than in adenomas (47.8% vs. 12.2%, p < 0.01). Even in adenoma components of CIAs, AP tended to be found more frequent than in adenomas (41.2% vs. 12.2%). The incidence of AP in adenoma components was similar to that in carcinoma components (35.3%) in CIAs. In conclusion, DNA aneuploidy in adenomas may be a marker of malignant potential.

[Diagnostic value of DNA ploidy in epithelial elevated lesions of the stomach].

Using flow cytometry, we evaluated the diagnostic usefulness of DNA aneuploidy in epithelial elevated lesions of the stomach. Four biopsy specimens were obtained from each lesion in 14 elevated early cancers, 21 adenomas, 37 hyperplastic polyps and 11 cases of chronic gastritis with intestinal metaplasia. All samples obtained from benign lesions indicated diploidy. DNA aneuploidy was detected in 12 lesions (85.7%) of early cancers. DNA indices ranged from 1.10 to 1.19 in six of 10 intramucosal cancers with DNA aneuploidy. Meanwhile, a total of two submucosally invasive cancers had stemlines with a DNA index of more than 2.00. Four early cancers, including two submucosally invasive ones, had multiple aneuploid stemlines. DNA aneuploidy is a useful marker of malignancy in epithelial elevated lesions of the stomach. A higher DNA index and multiple aneuploid stemlines may be possible markers of submucosal invasion in early cancer.