Molecular validation of the modified Vienna classification of colorectal tumors - PubMed (original) (raw)

Comparative Study

Molecular validation of the modified Vienna classification of colorectal tumors

Tamotsu Sugai et al. J Mol Diagn. 2002 Nov.

Abstract

Although the Vienna classification has been introduced to resolve discrepancies in histological diagnoses of colorectal tumors between Western and Japanese pathologists, practical applications of this classification scheme have been problematic because invasion of the lamina propria of tumor cells is often difficult to recognize. Therefore, the following refinements of the classification criteria are needed: category 3, low-grade adenoma/dysplasia; category 4, intramucosal borderline neoplasia; 4-a, high-grade adenoma/dysplasia; 4-b, well-differentiated adenocarcinoma; category 5, definite carcinoma; 5-a, intramucosal moderately-differentiated adenocarcinoma; and 5-b, submucosal carcinoma. We attempted to test whether molecular genetic alterations are related to the modified classification scheme and whether they may help to further categorize the various intramucosal neoplasia grades of colorectal tumors. Two-hundred-thirty-two colorectal tumors were examined using flow cytometric analysis of DNA content, polymerase chain reaction microsatellite assays, and single-strand conformational polymorphism assays to detect abnormalities of DNA content, chromosomal allelic loss, and Ki-ras and p53 gene mutations. Microsatellite instability (MSI) was also examined. Frequencies of genetic alterations and DNA aneuploid states increased with an increase in the grade assigned according to the modified Vienna classification. MSI was a rare event in colorectal adenomas and their frequency of MSI did not correlate with tumor grade. The combined genetic and DNA ploidy data support the conclusion that analysis of genetic alterations and DNA aneuploid states may help in appropriate categorization of colorectal tumors according to the modified Vienna scheme. In addition, MSI-positive tumors may represent a specific subtype of colorectal adenomas.

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Figures

Figure 1.

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.

Figure 2.

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.

Figure 3.

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.

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References

    1. Schlemper RJ, Riddell RH, Kato Y, Borchard F, Cooper HS, Dawsey SM, Dixon MF, Fenoglio-Preoser CM, Flejou J-F, Geboes K, Hattori T, Hirota T, Itabashi M, Iwafuchi M, Iwashita A, Kim YI, Kirchner T, Klimpfinger M, Koike M, Lauwers GY, Lewin KJ, Oberhuber G, Offner G, Price AB, Ribio CA, Shimizu M, Shimoda T, Sipponen P, Solcia E, Stolte M, Watanabe H, Yamabe H: The Vienna classification of gastrointestinal epithelial neoplasia. Gut 2000, 47:251-255 - PMC - PubMed
    1. Schlemper RJ, Itabashi M, Kato Y, Lewin KJ, Riddell RH, Shimoda T, Sipponen P, Stolte M, Watanabe H: Differences in the diagnostic criteria used by Japanese and Western pathologists to diagnose colorectal carcinoma. Cancer 1998, 82:60-69 - PubMed
    1. Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Nakamura Y, White R, Smits AMM, Bos JL: Genetic alterations during colorectal tumor development. N Engl J Med 1988, 319:525-532 - PubMed
    1. Fearon ER, Vogelstein B: A genetic model for colorectal tumorigenesis. Cell 1990, 61:759-767 - PubMed
    1. Miyaki M, Seki M, Okamoto M, Yamanaka A, Maeda Y, Tanaka K, Kikuchi R, Iwama T, Ikeuchi T, Tonomura A, Nakamura Y, White R, Miki Y, Utsunomiya J, Koike M: Genetic changes and histolopathological types in colorectal tumors from patients with familial adenomatous polyposis. Cancer Res 1990, 50:7166-7173 - PubMed

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