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Higher Frequency of Diploidy in Young-Onset Microsatellite-Stable Colorectal Cancer

Authors' Affiliations: Departments of ¹ Gastroenterology, ² Health Sciences Research, ³ Laboratory Medicine and Pathology, ⁴ Medical Genetics, and ⁵ Cancer Center Statistics, Mayo Clinic College of Medicine, Rochester, Minnesota

Requests for reprints: Lisa A. Boardman, Mayo Clinic College of Medicine, 200 First Street SW, Gonda 9 South, Rochester, MN 55905. Phone: 507-284-2175; Fax: 507-266-0350; E-mail: boardman.lisa{at}mayo.edu.

Purpose: Colorectal carcinoma (CRC) can be divided into two nonoverlapping groups: those that are chromosomally unstable but microsatellite stable (MSS CIN+) and those that are chromosomally stable but microsatellite unstable (MSI CIN–). However, a third group with neither chromosome nor microsatellite instability (MSS CIN–) makes a substantial contribution to the total CRC burden. The clinicopathologic features of MSS CIN– CRC are not well delineated. We assessed the relationship between age and chromosomal instability (CIN) status as measured by ploidy and allelic imbalance in a series of MSS tumors.

Experimental Design: We studied a prospectively collected series of CRC patients at Mayo Clinic Rochester. A total of 84 samples of MSS CRC in patients 50 years old were identified between 1994 and 1997. A consecutive series of 90 MSS CRC in patients 65 years old served as a comparison group. CIN status was assessed using two techniques: ploidy analysis by flow cytometry and small chromosome changes as measured by genomewide fractional allelic imbalance.

Results: CRC in the young-onset group was more likely to involve the rectum and to be high stage. MSS tumors in the young-onset group were more often diploid (46%) than those in older patients (26%; P = 0.006). This difference was maintained in the subset of MSS CRC that were high stage (42% versus 18%; P = 0.02) and in rectal cancers (50% versus 23%; P = 0.04).

Conclusion: A greater proportion of young patients with MSS CRC has diploid tumors than patients who develop MSS CRC over age 65.