01376-A: Immunohistochemical Detection of Retinoid Receptor Alpha (RARa) in Naturally Occurring Cases of Cutaneous Mast Cell Tumors in Dogs
Grant Status: Closed
Grant Amount: $1,975.64
Dr. Carlos H. de M. Souza, DVM, University of Missouri, Columbia
January 1, 2010 - December 31, 2010
Breed(s): -All Dogs
Disease(s): Mast Cell Tumors
Abstract Mast cell tumors (MCT) are the most common tumor of the skin in dogs. They represent up to 21% of all skin tumors in dogs. A variety of different breeds have been found to be predisposed to MCT including: boxers, Boston terriers, bull terriers, bullmastiffs, cocker spaniels, Staffordshire terriers, fox terriers, English bulldogs, dachshunds, Labrador retrievers, golden retrievers, beagles, pugs, schnauzer, shar-peis, and Weimaraners. The behavior of MCT varies widely and although cure can be achieved after wide surgical removal in the most benign forms, cure or even temporary control remains elusive in larger or highly malignant tumors. Clearly, additional treatment options are needed to control the most aggressive or most advanced stages of MCT. One possible new treatment is the use of vitamin A analogs, also known as retinoids. Retinoids have been used to treat a variety of cancers. One of the best examples is the use of the synthetic retinoid isotretinoin for the treatment of promyelocytic leukemia (PML) in people. In PML, the cells possess a genetic mutation that precludes their normal aging. These cells, in consequence, cannot stop dividing. Retinoids can overcome this abnormality, leading to response rates greater than 90% in PML patients. Today retinoids are also being used in prevention and treatment studies on skin cancer, head and neck cancer (HNC), thyroid, breast, and lung tumors, among others. Additionally, retinoid treatment is relatively safe and the few severe side effects are reversed by treatment discontinuation.
In dogs, retinoids have also been used to treat tumors of the skin, and only minimal side effects were observed. In a study of dogs with malignant lymphoma of the skin, treated with retinoids as single agents, the overall response rate was 42%. More recently, 2 independent groups showed that MCT respond to retinoid treatment in vitro and this response will occur if the cells have a specific retinoid receptor called RAR-?. In this scenario, retinoids enter the cell and attach to the receptor. The end result is a message sent from the DNA that makes the cell stop dividing or to program and execute its own death. The incidence of RAR? in canine MCT is unknown. Our study will detect the presence of RAR? receptors in naturally occurring MCT in dogs.
This preliminary work will lay the foundation for a larger study that will evaluate the effects of
synthetic retinoids for the treatment of MCT in dogs.