Topic Highlight
Copyright ©2014 Baishideng Publishing Group Inc.
World J Gastroenterol. Dec 14, 2014; 20(46): 17288-17296
Published online Dec 14, 2014. doi: 10.3748/wjg.v20.i46.17288
Table 1 Main pathways involved in the onset and development of colorectal cancer
Chromosomal instability or “suppressor” pathwayMicrosatellite instability or “mutator” pathwayCpG island methylator phenotype or “serrated” pathway
Percentage of CRC80%-85%10%-15%40%
Clinical characteristicsPredominant location of tumor in the distal colonPredominant location of tumor in the right colonPredominant location of tumor in the right colon
Better prognosisFemale sex
Histopathologic characteristicsNo lymphocytic reactionsLymphocytic reactionsLow-grade tumor differentiation
No mucinous featuresMucinous features
Good differentiationSignet ring cells
Low-grade tumor differentiation
Molecular characteristicsAneuploidy, polyploidy, loss of heterozygosityDiploidy, MSIMethylation of CpG islands
Main genes involvedAPC, P53, KRAS, C-MYC, DCC/SMAD4, TGFBR, PIK3CAMLH1, MSH2,BRAF, MSI
MSH6, PMS2,
TGF-βRII, IGFIIR,
MSH3 and BAX
Hereditary syndromesFamilial adenomatous polyposisLynch syndrome
Table 2 Main features of molecular classification
CategoryCRCCharacteristics
MolecularHistopathologicClinical
MSI/CIMP-high10%MLH1 methylationPoor differentationPredominant location of tumor in right colon
BRAF mutationsLymphocytic reactionElderly females
Mucinous/signet ring cellsSporadic MSI
MSI/CIMP-low/05%MMRLymphocytic reactionLS
Negative for BRAF mutationsMucinous features
No signet ring cells
Good or moderate differentation
MSS/CIMP-high5%-10%BRAF mutations and methylation of multiple other genesPoor differentationPredominant location of tumor in right colon
Signet ring cellElderly females
MSS/CIMP-low/075%-80%CINWell differentiatedPredominant location of tumor in distal colon
KRAS mutationsHeterogeneousMale sex
Table 3 Proportion of microsatellite instability in early-onset colorectal cancers series and their age of onset
StudyAge of CRC onset, yrPopulationMSI, n (%)
Losi et al[9] ≤ 45Unselected CRC surgical patients71 (19.7)
Liang et al[10] ≤ 40Unselected CRC surgical patients138 (40.5)
Perea et al[11] ≤ 45Unselected CRC surgical patients88 (13.6)
Jasperson et al[50]< 36Hereditary cancer registries96 (29.1)
Durno et al[51]< 25Familial cancer registry16 (72.7)
Farrington et al[52]< 30Cancer registries50 (47.5)
Antelo et al[66]< 50Cancer registry118 (22.9)