Summary:
Rapidly evolving treatment modalities for melanoma increases the need for reliable and informative biomarkers. H&E-determined mitotic activity and Ki67 index are both widely used cellular proliferation markers and thus used as prognostic markers in a variety of tumors including melanoma, breast, soft tissue, and neuroendocrine malignancies. H&E determination of mitotic activity is limited due to poor reproducibility and difficulties in distinguishing apoptotic bodies from true mitotic figures. The utility of Ki67 on the other hand, may suffer from its expression in non-mitotic phases of cell cycle. We have identified a newly discovered 4E-BP1 isoform p4E-BP1S83 whose expression is restricted to mitosis (Velasquez C. et al 2016). Further, we have developed a robust antibody reagent that can identify and accentuate mitotic cells in tissue section. This proposal will investigate the potential use of p4E-BP1S83 as a superior mitotic marker to improve melanoma classification and staging.