DNA content analysis of colorectal cancer defines a distinct ‘microsatellite and chromosome stable’ group but does not predict response to radiotherapy

Summary Colorectal cancers ( CRC ) are thought to have genetic instability in the form of either microsatellite instability ( MSI ) or chromosomal instability ( CIN ). Recently, tumours have been described without either MSI or CIN , that is, microsatellite and chromosome stable ( MACS ) CRC s. We investigated the (i) frequency of the MACS ‐ CRC s and (ii) whether this genotype predicted responsiveness to neoadjuvant chemoradiotherapy. To examine the frequency of MACS ‐ CRC s, DNA content (ploidy) was examined in 89 sporadic microsatellite‐stable CRC s using flow cytometry. The tumours were also screened for mutations in KRAS / BRAF / TP 53/ PIK 3 CA by QMC ‐ PCR . To examine the value of tumour ploidy in predicting response to chemoradiotherapy, DNA content was tested in a separate group of 62 rectal cancers treated with neoadjuvant chemoradiotherapy. Fifty‐one of 89 CRC s (57%) were aneuploid and 38 (43%) were diploid. There was no significant association between mutations in TP 53/ KRAS / BRAF / PIK 3 CA and ploidy. Testing of association between mutations revealed only mutual exclusivity of KRAS / BRAF mutation ( P  < 0.001). Of the 62 rectal cancers treated with neoadjuvant chemoradiotherapy, 22 had responded (Mandard tumour regression grade 1/2) and 40 failed to respond (Grade 3–5). Twenty‐five of 62 (40%) tumours were diploid, but there was no association between ploidy and response to therapy. We conclude that MACS ‐ CRC s form a significant proportion of microsatellite‐stable CRC s with a mutation profile overlapping that of CRC s with CIN . A diploid genotype does not, however, predict the responsiveness to radiotherapy.