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Flat and depressed lesions, sometimes called nonpolypoid, are believed to contribute disproportionately to the occurrence of postcolonoscopy cancers. To evaluate the molecular features of these lesions, investigators conducted a meta-analysis of 53 trials.
Compared with polypoid neoplasms, nonpolypoid neoplasms were less likely to have KRAS gene mutations (summary odds ratio, 0.14). The same trend was observed for adenomas but was not statistically significant.
In a subanalysis, depressed neoplasms were less likely than polypoid neoplasms to have KRAS mutations (summary OR, 0.12). The same trend was observed for slightly elevated neoplasms (Paris classification IIA) but was not statistically significant.
Lateral spreading tumors (LSTs) of nongranular type were less likely to have KRAS mutations compared with polypoid neoplasms (summary OR, 0.61).
The likelihood of KRAS mutations in LSTs of granular type was elevated but not statistically significant.
APC mutations were less frequent in nonpolypoid neoplasms than in polypoid neoplasms (summary OR, 0.42).
Compared with polypoid neoplasms, nonpolypoid neoplasms were more likely to have BRAF mutations (summary OR, 2.20).
The frequency of microsatellite instability did not differ between nonpolypoid and polypoid neoplasms, and data were insufficient to assess differences in hypermethylation and the CpG island methylator phenotype (CIMP).
Voorham QJM et al. Tracking the molecular features of nonpolypoid colorectal neoplasms: A systematic review and meta-analysis. Am J Gastroenterol 2013 Jul; 108:1042. (http://dx.doi.org/10.1038/ajg.2013.126)
Comment
These data indicate that compared with polypoid cancers, nonpolypoid cancers have a lower frequency of both KRAS mutations (particularly depressed lesions) and APC mutations. BRAF mutations are increased in nonpolypoid neoplasms, suggesting an association with the hypermethylation pathway, although this was not confirmed in studies evaluating microsatellite instability and CIMP.
A growing body of evidence suggests that colorectal cancer represents several general categories of molecular pathways (chromosomal instability pathway, serrated or hypermethylated pathway, and the Lynch pathway), each of which has clinical correlations with factors such as lesion shape, location in the colon, and types of precursor lesions. A modern colonoscopist should understand these general categories and their implications for detection and resection during colonoscopy.