The Scope E-Newsletter March 2010 Kestler and Bruker Receive Susan G. Komen Foundation Grant

Daniel Kestler, PhD, Assistant Professor, Human Immunology and Cancer Program (HICP), and Charles Bruker, MD, Pathology Resident, recently received notification of a three-year grant period totaling more than $575,000 in funds from the Susan G. Komen Foundation to develop an understanding of the Odontogenic Ameloblast associated protein (ODAM) expression in breast tumors as well as patients' humoral response to this protein. This study will provide the basis for the possible direct use of ODAM-based reagents in the assessment and treatment of breast cancers within the next decade.

ODAM is a protein that was first detected by Alan Solomon, MD, Director, HICP. It is produced within a rare calcifying epithelial odontogenic tumor and is the amyloid forming protein found with this tumor. Dr. Kestler, together with other HICP researchers, expressed recombinant ODAM and made antibodies to this protein. They found using immunohistochemical methods that ODAM was expressed within specific normal tissues, such as salivary gland and airway epithelium, and also within other epithelial cancers, including those of the breast, gastrointestinal tract and lung.

HICP investigators, along with Sabina Siddiqui, MD, Surgery Resident; Dr. Bruker; and Amber Patton, DO, Pathology Resident, immunohistochemically examined a significant number of slides for ODAM expression. These were breast cancer biopsies and resections identified through the University of Tennessee Cancer Center tumor registry and obtained from the Department of Pathology. This ODAM tumor expression was compared to patient staging and other reported clinicopathological data by Drs. Bruker and Siddiqui in conjunction with UT statisticians. The findings supported a relationship between ODAM expression and clinical stage as ODAM tumor-expression appears to correspond with better survival. These findings were recently presented at a national meeting and published in the American Surgeon.

HICP investigators had also observed and reported that late-stage breast cancer patients appear to possess anti-ODAM-specific serum antibody titers relative to normal females. This may support a possible relevant immunological response to ODAM in a portion of breast cancer patients. The proposed research will further investigate ODAM expression in breast tumors along with the presence of serum antibodies to ODAM in these patients in order to clarify any diagnostic, prognostic or possible therapeutic benefits of ODAM expression in tumor tissue or patient serum antibodies to ODAM.

"We plan to verify the importance of ODAM expression in tumor tissue," Dr. Kestler said. "We also want to determine the relationship of patient anti-ODAM antibody reactivity to clinical data including disease stage, survival, recurrence and cancer status."

Dr. Kestler said his partnership with the Surgery and Pathology residency programs has presented an opportunity to apply medical and molecular perspectives to important biomedical research that often has been limited to basic or clinical science. "Through such collaboration, everyone and everything involved, scientists, clinicians and the work, are enriched and better for the interaction."

Dr. Bruker added, "This is translational research. It serves as the bridge between clinicians and the basic sciences. This type of research has been less common in the past, and discoveries have been made at the bench that physicians were not aware of. Translational research brings these results to the patient."