Potential explanations for the observed differences in prognostic impact of nuclear InsR according to BMI include changes in methylations patterns (39), ligand levels (5, 23–25, 40), and altered intracellular receptor trafficking and recycling rates depending on ligand levels (41), as well as differential nuclear InsR suppression of the IGF1R promotor according to tumor ER status (16). Here, IGF1R is linked to neoplasm.