Intratumoral heterogeneity (ITH) may produce regional biases in genotype and phenotype evaluation in a single
tumor and may impede proper
cancer diagnosis. To evaluate the extent of ITH in
colorectal cancer (CRC) with
microsatellite instability (MSI), we obtained 4-7 biopsies from 39
CRCs followed by MSI analysis either using the Bethesda MSI evaluation system or
Promega system with 5 mononucleotide markers. We found decreased prevalence of MSI (+) by the
Promega system compared to the Bethesda system. The overall discordance between the two systems was 54 %. In contrast to the previous studies that had shown discordance only in low MSI (MSI-L), our results showed the discordance not only in MSI-L, but also in high MSI (MSI-H) cases. Among the MSI (+)
CRCs, ITH of MSI status was identified in 41.7 % of CRC by the Bethesda system and 22.2 % by the
Promega system. In terms of MSI markers, the ITH originated from dinucleotide markers in most cases (69 %), but it originated from mononucleotide markers (31 %) as well. Pooling of
DNA from a regional biopsy with MSI (+) with additional biopsies from stable MSI (MSS) showed that this approach was beneficial to increase the sensitivity of MSI detection. Our results indicate that ITH of MSI phenotype by the Bethesda system is more overestimated than previously identified. However, because there was considerable ITH of MSI subtypes and markers even by the
Promega system, our data suggest that analysis of MSI status in multiple regional biopsies is needed for a better evaluation of MSI status in CRC.