Analysis of Clinical and Molecular Parameters in MPNST
Abstract
Neurofibromatosis type 1 (NF1) is a progressive, genetic condition where one of the most common symptoms is a benign tumor called a neurofibroma. These arise from cells that normally function in nerves to keep electrical impulses moving smoothly. These can be on the skin, at the very ends of nerves (which don’t tend to get very big), or in deeper nerves (called plexiform neurofibroma). Some patients can have virtually no neurofibromas (on their skin or internally), while others can have thousands. A rare complication is development of a cancer called malignant peripheral nerve sheath tumor (MPNST), which usually evolves within an existing neurofibroma. MPNSTs are usually aggressive tumors and about half of patients don’t survive more than 5 years. The only approved therapies are surgery, chemotherapy, and radiation; we are lacking targeted, effective therapy. We also do not have formal guidelines for pathology diagnosis of MPNST. There are a couple of recommended tests, but they are far from perfect. Ideally, a pathology laboratory would take a biopsy from a concerning tumor and stain it with what we call “markers” to confirm an exact diagnosis and provide a guide to the doctor about whether those marker outcomes suggest better or worse survival. But since MPNSTs seem to be variable at almost every level that researchers have screened, it is difficult to develop the clinical tools. MPNSTs can occur in people who don’t have NF1, but we do not know whether those tumors behave similarly to those in NF1 patients. Pathologists try staining these with a probe called TP53, and the result is that some MPNSTs stain and some do not, and it has nothing to do with diagnosis of NF1 and does not predict severity well. There is not much else for the pathologists to use, and they are not uniform either. So we need improved tools for pathologists, especially a tool that is sensitive enough that it could possibly detect an early MPNST from a biopsy. In such cases, the tumors could just be surgically removed at an early stage, and patients might not need chemotherapy or radiation therapy as much. In the proposed work, we will first collect clinical data from MPNST cases at the University of Florida to evaluate whether any of the factors about the tumor or treatment have a good impact on survival. To try to understand the biological reasons behind the variability of this tumor (called heterogeneity), we will also stain slides from those tumors (from the same patients, using archived surgical samples from pathology). This staining to look at specific molecules will reveal the range of differences within the tumors. Comparison of the stain pattern with patient treatments and outcomes may help us develop better pathology markers and better predictability about how aggressive a specific MPNST might be (and maybe, what therapies might work best for that tumor). The markers we picked have the potential to be a new tool for diagnosis and prediction, but also may shed light on biological reasons for the tumor variability. This would be the basis for new basic research to identify “Achilles heels” of MPNST cancers that can lead to new therapies.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010355
Entities
People
- Margaret Wallace
Organizations
- United States Army
- University of Florida