University of Minnesota

Vaccine Associated Sarcoma Study

The  University of Minnesota is engaged in a study funded by the Vaccine Associated Sarcoma Task Force (VASTF). In the first phase of our study we have collected some very interesting data in regards to the possible pathogenesis of sarcoma tumor development and potential application for prognosis in these feline patients.

The focus of our study is based on a theory known as field cancerization. This theory was developed approximately 50 years ago when it was observed that the discrete islands of squamous cell carcinoma were found to arise within normal and dysplastic mucosa of the upper gastrointestinal and respiratory tract of humans. The hypothesis was then developed that this region of the anatomy has an increased risk of exposure to carcinogens and may therefore be at an increased risk for development of malignancies. Long term exposure to these carcinogens (i.e. tobacco smoke, exhaust fumes, chemical fumes and gasses) would result in an increased irritation in theses tissues resulting in increased cellular turnover and proliferation. This observation is supported by the occurrence of numerous premalignant lesions in the human oral cavity, esophagus, and lung.

When human patients are treated for cancers of the oral cavity and throat the biggest problem is the development of multiple primary and /or recurrent tumors. Despite microscopically clean margins local recurrence happens in up to 50% of these patients. In patients with these types of tumors it has been demonstrated that tissues adjacent to tumors that appear normal histologically have mutations present in an important tumor suppressor gene known as p53. This gene, p53, provides an important signal to mutated cells to die when abnormalities are detected in the DNA. When cells have abnormal or mutated p53 they do not detect these abnormalities and will grow and proliferate despite many defects within their DNA.

So where does this all apply to cats and vaccine associated tumors? Vaccine associated tumors provide a great model for study of the theory of field cancerization. The development of multiple synchronous tumors in a single patient and patients that have tumor recurrences following surgeries with histologically "clean" margins may be the result of malignant transformation of normal tissues by vaccine exposure. We are continuing to research potential mutations within the vaccine-associated tumors and the surrounding tissues. Preliminary results suggest that the normal appearing tissue surrounding the tumor may actually be exhibiting some characteristics of field cancerization. Mutations in the p53 gene have been identified in tumors and normal appearing tissues up to 5 cm away. These distant locations have been determined to appear normal on biopsy. It is too early to determine if these patients are at risk for development of tumor recurrence or new tumor development. Questions for further examination include why some feline patients develop the p53 mutation, identifying vaccines that may cause p53 mutations, and applying these findings to prevent tumor regrowth or recurrence.

Carrie A. Wood, DVM, ACVIM (oncology)
Asst. Clinical Specialist, Oncology
University of Minnesota
College of Veterinary Medicine

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