In the second model of tumor progression, up-regulation of proteins with high Ca2+ binding capacity, such as Calnexin or Binding immunoglobulin protein (BiP), as well as mutations in p53 sensory cell death machinery can account for the tumor types that had to down-regulate CRT expression early in their evolution because of their inability to resist its proimmunogenic function. This evidence concerns the gene TP53 and neoplasm.