Clinicopathologic and molecular characteristics of synchronous colorectal cancers:  heterogeneity of clinical outcome depending on microsatellite instability status of individual tumors.
BACKGROUND
The contribution of chromosomal instability, microsatellite instability, and epigenetic instability to the development of synchronous colorectal carcinomas is controversial.


OBJECTIVE
This study aimed to investigate the relative roles of microsatellite instability and epigenetic instability in the development of synchronous colorectal cancers.


METHODS
This was a retrospective study of medical records with histologic, immunohistochemical, and molecular examination of stored tissue samples.


METHODS
The study took place at Seoul National University Hospital, Korea.


METHODS
A total of 46 patients with synchronous colorectal cancers and 105 patients with solitary colorectal cancers were included.


METHODS
Clinicopathologic and molecular characteristics including microsatellite instability, mismatch repair gene expression, CpG island methylator phenotype, and mutation of KRAS and BRAF were analyzed.


RESULTS
Patients with synchronous tumors were more likely to be men than those with solitary tumors and had a tendency toward colocalization of individual tumors in the left or right colon. MSI-deficient cancers were more frequent in synchronous than in solitary cancers. The frequencies of CpG island methylator phenotype-high and KRAS and BRAF mutations were not different between synchronous and solitary cancers. No differences between synchronous cancers and solitary cancers were observed in overall survival or progression-free survival. Within the synchronous cancer group, patients with individual tumors discordant for microsatellite instability status had the worst clinical outcome, whereas those with individual tumors concordant for microsatellite instability-deficient status had the best clinical outcome.


CONCLUSIONS
The study was limited by its retrospective nature. Molecular analysis was performed only on cancerous lesions.


CONCLUSIONS
Our findings suggest that microsatellite instability plays a more important role than does epigenetic instability in the development of synchronous colorectal cancers, and that information regarding concordant or discordant microsatellite instability status between individual tumors might help to predict clinical outcome of synchronous colorectal cancers.
Department of Pathology, Seoul National University College of Medicine, 28 Yongon-dong, Songno-gu, Seoul, Korea.
Jeong M
JM
Bae
Nam-Yun
NY
Cho
Tae-You
TY
Kim
Gyeong H
GH
Kang
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D053843:DNA Mismatch Repair / Q000235:genetics; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation; D009378:Neoplasms, Multiple Primary / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D016019:Survival Analysis; D018631:ras Proteins / Q000235:genetics
D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins