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DNA aneuploidy is a biological marker of the oncogenic potential of colorectal adenomas. The accumulation of genetic alterations of cancer-related genes is also essential for colorectal carcinogenesis. However, it is unclear whether there is any relationship between these genetic alterations and the DNA ploidy of colon tumour cells in the progression of colorectal adenomas and early colorectal carcinomas. Here we have studied the DNA ploidy state and genetic alterations occurring in colorectal tumours using the crypt isolation technique. Crypts isolated from a total of 106 colorectal tumors (adenoma, 93; early carcinoma, 13) were examined using a combination of flow cytometric analysis of DNA content, polymerase chain reaction-microsatellite assay, and single-strand conformation polymorphism assay for evidence of chromosomal allelic imbalance (AI; 17p; 5q; 18q) or p53 gene mutation. In addition, we examined microsatellite instability (MSI) with BAT 26 primer sets. DNA multiploidy was infrequently detected in colorectal adenomas (15.1%), in contrast to early carcinomas (46.2%). There was a significant difference in the incidence of AI of chromosome 18q between diploid adenomas and aneuploid populations of multiploid adenomas (18.1% vs 57.1%, p = 0.0043). Mutation of p53 was also found more frequently in aneuploid populations of early multiploid colorectal carcinomas than in early diploid colorectal carcinomas (66.7% vs 0%, p = 0.021). MSI was found in only 2 of 93 adenomas, with no MSI detected in early colorectal cancers. The two MSI-positive adenomas were diploid. We subdivided multiploid adenomas into two groups: those with a low or a high DNA index (DI). The incidence of genetic alterations of high-DI adenomas did not differ from those of low-DI adenomas. Allelic imbalance involving loci on chromosome 18q and mutations of p53 seems to be associated with the progression of diploidy to multiploidy in colorectal tumours. On the other hand, MSI may be associated with the development of some diploid tumours. In addition, the incidence of genetic alterations in the colorectal adenomas that we examined appears to be independent of the tumour's DNA index.

DNA heterogeneity of colorectal carcinomas has been investigated by flow cytometry, most studies have focused on the clinical usefulness of DNA ploidy analysis. Since cancers consist of predominant subclones with proliferative advantage due to clonal expansion, we attempted to analyse the clonal expansion of colorectal carcinomas within a tumour by measuring DNA ploidy. The DNA ploidy and heterogeneity of multiple fresh samples obtained from 164 colorectal adenocarcinomas were analysed by flow cytometry. Each tumour was divided into an average of six specimens, which were analysed separately. For 146 of the tumours (89%) at least one DNA aneuploid population was found within the cancer tissue examined. DNA multiploidy was detected in 26 cases (17.8%) among the cancers with aneuploidy. Based on the DNA index (DI), hypertriploid aneuploidy (1.7

There are differing views between Western and Japanese pathologists on the use of histological criteria to classify gastrointestinal tumors. It is therefore a priority to create a new histological classification of the stomach in order to resolve the confusion. Expression patterns were examined of mucin (MUC2, CD10, MUC5AC, pyloric gland-type mucin), p53 protein, and Ki-67 in tumor cells according to the following new classification system for differentiated-type intramucosal neoplastic lesions of the stomach, based on nuclear atypia: borderline neoplasia (adenoma (including dysplasia), indefinite tumor of adenoma or low-grade cancer, and low-grade cancer) and definite carcinoma (intermediate cancer, and high-grade cancer). The resulting grades were: adenoma, 23; indefinite tumor for adenoma or low-grade cancer, 6; low-grade cancer, 28; intermediate cancer, 48; high-grade cancer, 20. While the frequency of intestinal-type borderline neoplasias was higher than that of definite carcinomas, the mixed-type of definite carcinomas occurred with higher frequency than borderline neoplasias. The p53 protein overexpression and the Ki-67-positive rate increased with an increase in the grade assigned according to the new classification. The correlated expression levels of p53 protein, Ki-67, and various mucins, support the conclusion that this classification of intramucosal neoplastic lesions is useful for obtaining a consensus diagnosis of gastric intramucosal neoplasia between pathologists and gastrointestinal clinicians.

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