Morphology of sporadic colorectal cancer with DNA replicationerrors

Background—Up to 15% of colorectal cancers arecharacterised by DNA microsatellite instability (MIN), shown by thepresence of DNA replication errors (RERs).
Aims—To identify pathological features that arediscriminating for colorectal cancer (CRC) showing extensive MIN.
Subjects—A prospective series of 303 patientswith CRC and no family history of either familial adenomatous polyposisor hereditary non-polyposis colorectal cancer.
Methods—DNA was extracted from fresh tissuesamples and the presence of MIN was studied at nine loci that includedTGFβRII, IGFIIR, and BAX. The 61 cases showing RERs were comparedwith 63 RER negative cases with respect to a comprehensive set ofclinical and pathological variables. Predictive utility of thevariables was tested by decision tree analysis.
Results—Twenty seven patients with CRC showedextensive RERs (three loci or more) (RER+) and 34 had limited RERs only(28= one locus; 6 = two loci) (RER+/−), yielding a bimodaldistribution. RER+ cancers differed from RER− and RER+/− cases.Tumour type (adenocarcinoma, mucinous carcinoma, and undifferentiatedcarcinoma) (p=0.001), tumour infiltrating lymphocytes (p=0.001), andanatomical site (p=0.001) were the most significant of thediscriminating variables. Algorithms developed by decision treeanalysis allowed cases to be assigned to RER+ versus RER− and +/−status with a global sensitivity of 81.5%, specificity of 96%, andoverall accuracy of 93%.
Conclusion—Pathological examination of CRC allowsassignment of RER+ status; assignment is specific and relativelysensitive. Conversely RER− and RER+/− CRC are indistinguishable.

Keywords:colon; rectum; colorectal cancer; DNA replicationerrors; morphology; microsatellite instability