MRC1 and neoplasm: Compared with the expression loss of a single MMR protein/heterodimer, a double-negative MMR protein IHC pattern is characterized by a higher level of non-synonymous variants, unstable microsatellite loci, a significant increase in TMB, and an increased number of tumor-infiltrating lymphocytes, which are also characterized by a substantial population of exhausted CD8+ lymphocytes (25).