Microsatellite instability as a marker in predicting metachronous multiple colorectal carcinomas after surgery: a cohort-like study.
OBJECTIVE
In case-control studies, it was reported that microsatellite instability might be helpful in predicting the development of metachronous multiple colorectal cancers. The purpose of this cohort-like study was to determine whether microsatellite instability is a novel independent marker in predicting metachronous colorectal carcinomas after colorectal cancer surgery.


METHODS
Three hundred twenty-eight colorectal carcinoma patients were surveyed by periodic colonoscopy for at least three years after surgery. Among these, DNA from paraffin-embedded sections was available for 272 cases. DNA of these cases was studied for six microsatellite markers (five dinucleotide repeats, one mononucleotide repeat). Microsatellite instability phenotype was defined as alterations in one or more loci.


RESULTS
Median follow-up period was 74 months, and the median number of colonoscopies was 4.6. The percentage of microsatellite instability-positive cases was 26.4 percent (72/272). Seventeen metachronous colorectal carcinomas were detected during the follow-up period. Incidences of metachronous colorectal carcinomas in microsatellite instability-positive and microsatellite instability-negative cases were 15.3 and 3 percent, respectively (P < 0.001). The cumulative five-year incidence of metachronous colorectal carcinomas was significantly higher in microsatellite instability-positive cases than in microsatellite instability-negative cases (12.5 vs. 2.5 percent, P < 0.0001). Logistic regression analysis of the relationship between incidence of metachronous colorectal carcinomas and possible risk factors (namely, coexistence of adenoma at the time of surgery, family history of colorectal carcinoma, history of extracolonic malignancy, and microsatellite instability status) showed that microsatellite instability and coexistence of adenoma were significant independent risk factors for the occurrence of metachronous colorectal carcinomas, with values of P = 0.001 and 0.02, respectively.


CONCLUSIONS
These data indicate that microsatellite instability can be regarded as a novel independent and important marker for predicting the development of metachronous colorectal carcinoma after surgery.
Shitoh
Kazuhisa
K
Department of Surgery, Jichi Medical School, Tochigi-ken, Japan.
Konishi
Fumio
F
Miyakura
Yasuyuki
Y
Togashi
Kazutomo
K
Okamoto
Tomomi
T
Nagai
Hideo
H
D002277:Carcinoma / Q000235:genetics* / Q000601:surgery*; D015331:Cohort Studies; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000601:surgery*; D005500:Follow-Up Studies; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics*; D016609:Neoplasms, Second Primary / Q000209:etiology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D012307:Risk Factors; D013997:Time Factors