The Karen Wyckoff Sarcoma Foundation is dedicated to Sarcoma Cancer research, support and education...and the fight to find a cure.
Quantification of four biomarkers that demonstrate clinical correlations in aggressive fibromatosis
Project Title: "Quantification of four biomarkers that demonstrate clinical correlations in aggressive fibromatosis"
Principal Investigator Name: Amy P.N. Skubitz, Ph.D., Laboratory Medicine and Pathology
RIS 2011 funding: $21,366
Project Summary: In earlier studies, we discovered four genes (ADAM12, WISP-1, SOX-11, and FAP) that were expressed at high levels in patients with Aggressive Fibromatosis (AF) or desmoid tumor. We hypothesize that AF tumors and other types of sarcomas can be classified into two groups based upon gene expression patterns: those with a high vs. low rate of recurrence. To verify this, we examined tumors from AF patients for the presence of proteins corresponding to these genes. In preliminary studies, we used antibodies against our four proteins to stain tissues from 12 AF patients. These four proteins were present in areas of tumors that appeared more "active" or "aggressive".
In this project, we will quantify the staining of our four proteins in 27 cases of AF. This will be accomplished by digitally scanning the slides and quantifying the level of staining in the tumors by use of state of-the-art computer analysis. We will then demonstrate a relationship between the expression of these proteins and the clinical outcome of the patients.
This study is significant for the field of sarcomas for two reasons. First, AF has no well-defined treatment and its biology is not understood. Second, our results suggest that some of the genes involved in AF may predict how sarcomas grow. Therefore, these genes may be potential drug targets for sarcomas. In future studies, we will: determine whether these proteins are unregulated in other types of sarcomas, discover the functional role of these proteins in sarcomas, and develop inhibitors for therapeutically treating sarcomas.
Name(s) of project collaborator(s), academic departments/schools, and role in the project:
- Carlos Manivel, M.D., Dept. Lab. Med. & Path., Role in project: Pathologist to oversee verification of immunohistochemical (IHC) scoring of tissues.
- Edward Cheng, M.D., Dept. Orthopaedic Surgery, Role in project: Orthopedic surgeon who will correlate IHC data with clinical outcome.
- Keith Skubitz, M.D., Dept of Medicine, Division of Hematology, Oncology, and Transplantation; Role in project: Oncologist to correlate IHC data with chemotherapy response and clinical outcome.
- Stephen Schmechel, M.D., Ph.D., Dept Lab. Med. & Path.; Director of BioNet, Pathologist to oversee the digital analysis and optimize the Genie software classifier