Clinical implications of microsatellite instability in colorectal cancers.
BACKGROUND
Microsatellite instability (MI) has been reported in some sporadic colon tumors and in cases of hereditary nonpolyposis colorectal cancer (HNPCC). The criteria for HNPCC have not been fully defined, and clinical criteria are used to identify as many HNPCC patients as possible. To clarify the conformity of these criteria with the identification of eligible HNPCC cases, we analyzed MI in HNPCC patients diagnosed using clinical criteria.


METHODS
Genomic DNA was extracted from surgical specimens of 56 colorectal cancers, including 36 from patients diagnosed with HNPCC using the clinical criteria. We analyzed four microsatellite loci using 32P-labeled primers.


RESULTS
Among HNPCC patients diagnosed using clinical criteria, patients who were positive for MI accounted for 62% of Group A (a confirmed group) and 35% of Group B (a high risk group); only 5% of randomly selected colorectal cancer patients (Group C), were positive for MI. Furthermore, MI-positive tumors were found in patients who had a tendency for tumors to involve the right side of the colon, an association with cancers in other organs, a lower incidence of p53 protein positivity, and a higher proportion of poorly differentiated cancers.


CONCLUSIONS
The presence of MI, in concert with modified clinical criteria, may identify legitimate cases of HNPCC in patients who might otherwise be excluded by the minimum criteria.
Muta
H
H
Pathology Division, National Cancer Center, Research Institute, Tokyo, Japan.
Noguchi
M
M
Perucho
M
M
Ushio
K
K
Sugihara
K
K
Ochiai
A
A
Nawata
H
H
Hirohashi
S
S
D017668:Age of Onset; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D005819:Genetic Markers; D006801:Humans; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D009378:Neoplasms, Multiple Primary / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D004273:DNA, Neoplasm; D005819:Genetic Markers; D016159:Tumor Suppressor Protein p53