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.
Figures
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.
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.
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.
Similar articles
- Analysis of genetic alterations, classified according to their DNA ploidy pattern, in the progression of colorectal adenomas and early colorectal carcinomas.
Sugai T, Takahashi H, Habano W, Nakamura S, Sato K, Orii S, Suzuki K. Sugai T, et al. J Pathol. 2003 Jun;200(2):168-76. doi: 10.1002/path.1340. J Pathol. 2003. PMID: 12754737 - Relationship between genetic alterations and prognosis in sporadic colorectal cancer.
Chang SC, Lin JK, Yang SH, Wang HS, Li AF, Chi CW. Chang SC, et al. Int J Cancer. 2006 Apr 1;118(7):1721-7. doi: 10.1002/ijc.21563. Int J Cancer. 2006. PMID: 16231316 - Frequent p53 gene mutations in serrated adenomas of the colorectum.
Hiyama T, Yokozaki H, Shimamoto F, Haruma K, Yasui W, Kajiyama G, Tahara E. Hiyama T, et al. J Pathol. 1998 Oct;186(2):131-9. doi: 10.1002/(SICI)1096-9896(1998100)186:2<131::AID-PATH158>3.0.CO;2-1. J Pathol. 1998. PMID: 9924427 - Analysis of Ki-ras gene mutations associated with DNA diploid, aneuploid, and multiploid colorectal carcinomas using a crypt isolation technique.
Sugai T, Habano W, Nakamura S, Jiao YF, Higuchi T, Inomata M, Chiba T. Sugai T, et al. Cytometry. 2001 Dec 15;46(6):345-50. doi: 10.1002/cyto.10033. Cytometry. 2001. PMID: 11754204 - Sequence of molecular genetic events in colorectal tumorigenesis.
Laurent-Puig P, Blons H, Cugnenc PH. Laurent-Puig P, et al. Eur J Cancer Prev. 1999 Dec;8 Suppl 1:S39-47. Eur J Cancer Prev. 1999. PMID: 10772417 Review.
Cited by
- Analysis of the expression of cancer-associated fibroblast- and EMT-related proteins in submucosal invasive colorectal cancer.
Sugai T, Uesugi N, Kitada Y, Yamada N, Osakabe M, Eizuka M, Sugimoto R, Fujita Y, Kawasaki K, Yamamoto E, Yamano H, Suzuki H, Matsumoto T. Sugai T, et al. J Cancer. 2018 Jun 23;9(15):2702-2712. doi: 10.7150/jca.25646. eCollection 2018. J Cancer. 2018. PMID: 30087711 Free PMC article. - Comprehensive molecular analysis based on somatic copy number alterations in intramucosal colorectal neoplasias and early invasive colorectal cancers.
Sugai T, Eizuka M, Habano W, Fujita Y, Sato A, Sugimoto R, Otsuka K, Yamamoto E, Matsumoto T, Suzuki H. Sugai T, et al. Oncotarget. 2018 May 1;9(33):22895-22906. doi: 10.18632/oncotarget.25112. eCollection 2018 May 1. Oncotarget. 2018. PMID: 29796160 Free PMC article. - Overexpression of xeroderma pigmentosum group C decreases the chemotherapeutic sensitivity of colorectal carcinoma cells to cisplatin.
Zhang Y, Cao J, Meng Y, Qu C, Shen F, Xu L. Zhang Y, et al. Oncol Lett. 2018 May;15(5):6336-6344. doi: 10.3892/ol.2018.8127. Epub 2018 Feb 27. Oncol Lett. 2018. PMID: 29616110 Free PMC article. - Molecular alterations in colorectal adenomas and intramucosal adenocarcinomas defined by high-density single-nucleotide polymorphism arrays.
Eizuka M, Sugai T, Habano W, Uesugi N, Takahashi Y, Kawasaki K, Yamamoto E, Suzuki H, Matsumoto T. Eizuka M, et al. J Gastroenterol. 2017 Nov;52(11):1158-1168. doi: 10.1007/s00535-017-1317-2. Epub 2017 Feb 14. J Gastroenterol. 2017. PMID: 28197804 Free PMC article. - Analysis of molecular alterations in laterally spreading tumors of the colorectum.
Sugai T, Habano W, Takagi R, Yamano H, Eizuka M, Arakawa N, Takahashi Y, Yamamoto E, Kawasaki K, Yanai S, Ishida K, Suzuki H, Matsumoto T. Sugai T, et al. J Gastroenterol. 2017 Jun;52(6):715-723. doi: 10.1007/s00535-016-1269-y. Epub 2016 Oct 4. J Gastroenterol. 2017. PMID: 27704264
References
- 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
- 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
- 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
- Fearon ER, Vogelstein B: A genetic model for colorectal tumorigenesis. Cell 1990, 61:759-767 - PubMed
- 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
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous