Molecular Validation of the Modified Vienna Classification of Colorectal Tumors Tamotsu Sugai, Wataru Habano, Noriyuki Uesugi, Yu-Fei Jiao, Shin-ichi.

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Molecular Validation of the Modified Vienna Classification of Colorectal Tumors Tamotsu Sugai, Wataru Habano, Noriyuki Uesugi, Yu-Fei Jiao, Shin-ichi Nakamura, Kimihiko Sato, Toshimi Chiba, Motohiro Ishii The Journal of Molecular Diagnostics Volume 4, Issue 4, Pages 191-200 (November 2002) DOI: 10.1016/S1525-1578(10)60703-9 Copyright © 2002 American Society for Investigative Pathology and Association for Molecular Pathology Terms and Conditions

Figure 1 a and b: Low-grade dysplastic adenoma (category 3). 1-b was treated as moderate dysplasia according to the previous classification scheme. c: High-grade dysplastic adenoma showing irregular glands and hyperchromatic nuclei (category 4-a). d: Well-differentiated adenocarcinoma showing severe irregular branching of glands and hyperchromatic nuclei (category 4-b). e: Moderately-differentiated adenocarcinoma (category 5-a) showing higher cellular and structural atypia (cribriform pattern) than the well-differentiated adenocarcinoma. The Journal of Molecular Diagnostics 2002 4, 191-200DOI: (10.1016/S1525-1578(10)60703-9) Copyright © 2002 American Society for Investigative Pathology and Association for Molecular Pathology Terms and Conditions

Figure 2 Frequencies of genetic alterations in colorectal adenomas and carcinomas. Frequencies of 17p, 18q, 8p, and 22q allelic losses and mutations of p53 and Ki-ras genes in category 4 tumors are significantly higher than are those of category 3 tumors. The frequencies denoted at the top of the column indicate those frequencies (%) showing allelic loss or mutations. The Journal of Molecular Diagnostics 2002 4, 191-200DOI: (10.1016/S1525-1578(10)60703-9) Copyright © 2002 American Society for Investigative Pathology and Association for Molecular Pathology Terms and Conditions

Figure 3 Analysis of allelic losses of chromosomal loci on chromosomes 17p, 5q, and 18q and p53 and Ki-ras gene mutation in high-grade dysplastic adenomas (category 4-a). a and b: Histological features of high-grade dysplastic adenoma. c: DNA histogram indicates a diploid cell. d–f: Electrophoregram of allelic losses at 5q, 17p, and 18q chromosomal loci. Arrows show the two alleles for each chromosomal locus. 5q allelic losses were found in this adenoma. In addition, 1p, 8p, and 22q allelic losses were not observed (electrophoregram not shown). g: A SSCP analysis of the p53 gene (exons 5–8). Arrows show the two normal alleles for each exon. An anomalously migrating band is seen corresponding to exon 7 (arrowheads). h and i: DNA sequence showing p53 and Ki-ras gene mutations. A CGC to CAG transition in codon 248 was found in h. In i, a GGT to GTT transversion occurred in codon 12 (sequenced by reverse primer). N, normal; T, tumor. The Journal of Molecular Diagnostics 2002 4, 191-200DOI: (10.1016/S1525-1578(10)60703-9) Copyright © 2002 American Society for Investigative Pathology and Association for Molecular Pathology Terms and Conditions