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Dis Colon Rectum. 2002 Feb;45(2):219-28.

Comparison of clinicopathologic characteristics and genetic alterations between microsatellite instability-positive and microsatellite instability-negative sporadic colorectal carcinomas in patients younger than 40 years old.

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1
Department of Pathology, University of Ulsan College of Medicine, Seoul, Korea.

Abstract

PURPOSE:

Many studies have demonstrated that sporadic microsatellite instability-positive colorectal cancers share several clinicopathologic features with hereditary nonpolyposis colorectal cancers, including right-sided location, young age of onset, characteristic histomorphologic features, and a good prognosis. The aim of this study was to define distinct clinicopathologic features of sporadic microsatellite instability-positive colorectal cancers and to compare genotypic characteristics between microsatellite instability-positive and microsatellite instability-negative colorectal cancers in a young group.

METHODS:

We analyzed 61 cases of young patients (<40 years old) with colorectal cancers for microsatellite instability at five mononucleotide and three dinucleotide repeats, loss of heterozygosity at APC and DCC, and K-ras and p53 mutations. Microsatellite instability status was correlated with molecular genetic factors and clinicopathologic parameters.

RESULTS:

Microsatellite instability positivity was detected in 19 (31.1 percent) of 61 cases. Allelic alterations in TGFbetaRII, BAX, and IGFIIR were observed exclusively in microsatellite instability-positive tumors (63.1, 26.3, and 26.3 percent, respectively). Microsatellite instability-positive tumors exhibited a lower frequency of the p53 mutation (10.5 percent) than microsatellite instability-negative tumors (47.6 percent; P < 0.05). However, microsatellite instability status was not associated with APC or DCC allelic deletion or with the K-ras mutation. Microsatellite instability-positive colorectal cancers exhibited a proclivity toward proximal location, expansive growth pattern, and large tumor size (P < 0.05). Microsatellite instability-positive colorectal cancers had lower preoperative serum carcinoembryonic antigen levels (P < 0.05), a less advanced stage at presentation (P < 0.05), and a tendency toward better prognosis (P = 0.051) than microsatellite instability-negative colorectal cancers. However, there was no difference between microsatellite instability-positive and microsatellite instability-negative colorectal cancers regarding gross features, tumor grade, and extracellular mucin production.

CONCLUSION:

These results suggest that sporadic microsatellite instability-positive colorectal cancers in young patients have different histomorphologic features from microsatellite instability-negative colorectal cancers and hereditary nonpolyposis colorectal cancers, some overlap of genetic alterations on multistep carcinogenesis with microsatellite instability-negative colorectal cancers, and a tendency for better prognosis.

PMID:
11852336
[Indexed for MEDLINE]
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