Higher frequency of diploidy in young-onset microsatellite-stable colorectal cancer.
OBJECTIVE
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.


METHODS
We studied a prospectively collected series of CRC patients at Mayo Clinic Rochester. A total of 84 samples of MSS CRC in patients <or=50 years old were identified between 1994 and 1997. A consecutive series of 90 MSS CRC in patients >or=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).


CONCLUSIONS
A greater proportion of young patients with MSS CRC has diploid tumors than patients who develop MSS CRC over age 65.
Boardman
Lisa A
LA
Department of Gastroenterology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA. boardman.lisa@mayo.edu
Johnson
Ruth A
RA
Petersen
Gloria M
GM
Oberg
Ann L
AL
Kabat
Brian F
BF
Slusser
Joshua P
JP
Wang
Liang
L
Morlan
Bruce W
BW
French
Amy J
AJ
Smyrk
Thomas C
TC
Lindor
Noralane M
NM
Thibodeau
Stephen N
SN
D000328:Adult; D017668:Age of Onset; D000368:Aged; D022981:Allelic Imbalance; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004247:DNA / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D004171:Diploidy; D005260:Female; D005434:Flow Cytometry; D005787:Gene Frequency; D005819:Genetic Markers; D042822:Genomic Instability; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011003:Ploidies; D011446:Prospective Studies
D004273:DNA, Neoplasm; D005819:Genetic Markers; D004247:DNA