Validation of a Tissue Microarray as a Useful Technique for Assessing Diagnostic and Predictive Tissue Biomarkers in Canine Diffuse Large B-cell Lymphoma
Fellow: W. Shane Sills
Mentor: Kristy Richards
DESCRIPTION (provided by applicant):
Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid neoplasm in both humans and dogs. Studies have demonstrated that the canine entity shares numerous clinicopathologic and molecular similarities, and further characterization of canine DLBCL would facilitate the development of a strong animal model of disease, as well as providing the means to develop new therapies in both human and veterinary medicine. Tissue microarrays (TMA) are a useful means of characterizing molecular biomarkers in numerous cases in a single experiment. While these are implemented in human medicine, a tissue microarray for canine DLBCL has not been established. The first aim of this proposal is to develop a valid TMA for characterizing DLBCL in dogs. Small cores of tissue from formalin-fixed, paraffin embedded tissues obtained from dogs seen at Cornell University Hospital for Animals and Cornell University Veterinary Specialists that were processed as diagnostic samples will be obtained and placed in the TMA template. A panel of immunohistochemical stains routinely used by the Animal Health Diagnostic Center will be applied to the TMA, and results will be compared to the original diagnostic report and assessed for agreement. We suspect the TMA to offer nearly 100% agreement with the original samples, indicating similar sensitivity and specificity.
In addition to routine screening, a TMA can be a valuable tool in characterzing new, potentially prognostically significant biomarkers. One such marker that has been characterized in humans is CD25, the alpha chain of the interleukin-2 receptor. After validating an anti-CD25 antibody in canine tissues, we characterize the prognostic significance of CD25 expression in canine DLBCL by comparing levels of expression to the clinical outcome, using Kaplan-Meier survival curves. We hypothesize that, similar to humans, CD25 expression will negatively correlate with survival time.