Fig. 2

Mismatch repair deficiency due to concurring MLH1/PMS2 loss is a prevalent feature of naturally occurring CRC in rhesus macaques and results in functional microsatellite instability. Exemplary IHC staining of CRC_1 for MMR proteins A MLH1, B MSH2, C MSH6, and D PMS2. The consistent nuclear expression of these proteins in healthy colon and infiltrating lymphocytes served as an internal positive control. As clearly depicted, MLH1 and PMS2 staining was lost in the neoplastic cells but MSH2 and MSH6 were highly expressed. E This pattern of MLH1/PMS2 loss was observed cohort-wide in all 24 rhesus CRCs. MSH2 expression was maintained in 23/24 CRCs and MSH6 expression was present in all 24/24 CRCs. The emphasized mismatch repair deficiency translates to an instable genetic phenotype as corroborated by the widespread microsatellite instability. In summary, 13/16 CRCs were classified as MSI-high (≥ 2 unstable loci), 3/16 as MSI-low (1 unstable loci), and none as MSS