Journal Article

Colorectal cancer without high microsatellite instability and chromosomal instability—an alternative genetic pathway to human colorectal cancer

Reiping Tang, Chung Rong Changchien, Meng-Chih Wu, Chung-Wei Fan, Kwang-Wen Liu, Jinn-Shiun Chen, Huei-Tzu Chien and Ling-Ling Hsieh

in Carcinogenesis

Volume 25, issue 5, pages 841-846
Published in print May 2004 | ISSN: 0143-3334
Published online May 2004 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh074
Colorectal cancer without high microsatellite instability and chromosomal instability—an alternative genetic pathway to human colorectal cancer

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At least two forms of genomic instability have been described in colorectal cancers (CRCs): microsatellite instability (MIN), which is characterized by a high frequency of microsatellite instability (MSI-H) and chromosomal instability (CIN), which is characterized by losses and gains of chromosomes (aneuploidy), as well as chromosome rearrangements. Morphological and molecular heterogeneity within MIN(−) CRCs have been described, but the distinctions between MIN(−) tumors with CIN and those without CIN remain largely unknown. We studied 179 colorectal cancers to elucidate the clinicopathological characteristics and molecular events in CRCs arising along these pathways. Loss of heterozygosity, MIN, DNA content, mutation of p53 and K-ras, and expression of p53, hMLH1 and hMSH2 were examined. We found that a subtype of tumors (17%) with MIN(−) and CIN(−), differed from MIN(−)CIN(+) tumors with respect to clinicopathological and genetic characteristics. This subtype was associated with a greater frequency of poorly differentiated and/or mucinous tumors (26%). This subtype of tumors had an extremely low p53 gene mutation rate (11%) and a relatively high p53 protein accumulation rate (55%). The dissociation between the p53 gene mutation and protein accumulation suggests that stabilization of p53 protein in the absence of p53 gene mutation may be an important event on a distinct pathway.

Keywords: CIN, chromosomal instability; CRC, colorectal cancer; IHC, immunohistochemistry; LOH, losses of heterozygosity; MIN, microsatellite instability; MSI-H, high frequency of microsatellite instability

Journal Article.  4471 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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