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JMD 2002, Vol. 4, No. 4
Copyright © 2002 American Society for Investigative Pathology & Association for Molecular Pathology

Molecular Validation of the Modified Vienna Classification of Colorectal Tumors

Tamotsu Sugai*, Wataru Habano*, Noriyuki Uesugi*, Yu-Fei Jiao*, Shin-ichi Nakamura*, Kimihiko Sato{dagger}, Toshimi Chiba{dagger} and Motohiro Ishii{dagger}

From the Division of Pathology, * Central Clinical Laboratory and the First Department of Internal Medicine, {dagger} School of Medicine, Iwate Medical University, Morioka, Japan

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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T. Sugai, W. Habano, Y.-F. Jiao, M. Tsukahara, Y. Takeda, K. Otsuka, and S.-i. Nakamura
Analysis of Molecular Alterations in Left- and Right-Sided Colorectal Carcinomas Reveals Distinct Pathways of Carcinogenesis: Proposal for New Molecular Profile of Colorectal Carcinomas
J. Mol. Diagn., May 1, 2006; 8(2): 193 - 201.
[Abstract] [Full Text] [PDF]


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Copyright © 2002 by the American Society for Investigative Pathology and the Association for Molecular Pathology.