Kendal Jensen and Dr. Kim O’Neill, Department of Microbiology and Molecular Biology
Each year in the United States there are over one million cases of nonmelanoma skin cancer. Detection of metastatic skin cancer requires skill and careful consideration of clinical and histologic features. An accurate and specific stain for early, definitive diagnosis of metastatic skin cancer would be a useful tool for clinicians. Investigations using antibodies against tumor-specific antigens (TSAs) as prognostic indicators in cancer are ongoing. A novel TSA, Thymidine Kinase 1 (TK1) has been discovered for a variety of solid tumors. This last year in Kim O’Neill’s lab I investigated the use of an antibody against TK1 for use in diagnosis of skin cancer.
Skin cancers from various patients at the Central Utah Clinic and Cole Diagnostics were donated to me for this project. Various forms of skin cancer were tested for the presence of TK1 and compared to pathologically-diagnosed aggressivity. Confocal microscopy was used to visualize formalin-fixed keratinocyte cells (HaCaT) which we stained with our monoclonal. Cells were stained with both primary and secondary antibodies and a control was stained with secondary only. 3-D images of the keratinocytes were achieved using confocal-microscopic software.
Promising results were achieved from this study. In a metastasizing melanoma, (The most aggressive and deadly skin cancer) the cancer showed strong positive staining for the presence of TK1. This indicates that TK1 may play a role in diagnosing skin cancer. In the future TK1 may be an effective treatment for human cancer, including but not limited to skin cancer. In 1975 Kohler and Milstein published a paper describing the development of hybridomas. Since then there has been increasing interest in the production of monoclonal antibodies (Mabs). These antibodies can be genetically engineered (humanization) so as to bypass the human immune system. Although we have not humanized our antibody it is possible that the antibody can be humanized and used as a cancer therapy. It is also unclear why TK1 would be located on the surface of skin cancer cells but this finding suggests that an anti-TK1 antibody would be a likely immunotherapy. This indicates that TK1 may play additional roles in cancers and not limited to skin cancer. Future studies on cancer should include TK1 as an immunotherapy and stain for various types of cancer. In the future, doctors may be able to monitor the prognosis of patients by following their TK1 levels.
This method is relatively simple and cost-effective. TK1 immunostaining would alleviate the ambiguity that a pathologist experiences when looking at cancerous tissue under the microscope. Further research considering patient prognosis needs to be conducted with clinical trials in order to verify this technique, but these encouraging data indicate that TK1 directly corresponds with skin cancer progression.
I was very excited to do this study. I presented at the Annual National Meeting for the American Academy for Cancer Research (The world’s largest cancer-research meeting), and was received very well. I have written the results and am currently submitting for publication. I am further investigating TK1 and skin cancer.