Serum TK1 activity and SAA concentration as biomarkers to differentiate lymphoma from gastrointestinal disease in cats

Abstract: Alimentary lymphoma is one of the most common malignant neoplasms in the gastrointestinal (GI) tract in cats. Since the clinical signs often are identical to those of inflammatory bowel disease (IBD), and the findings on diagnostic imaging and endoscopic mucosal biopsies overlap, invasive biopsy sampling from the GI tract is needed to be able to differentiate these two diseases from each other. Thymidine kinase 1 (TK1) is a cell cycle specific cytosolic enzyme involved in DNA synthesis and cell repair, and is commonly used as a tumor biomarker in human oncology since the TK1 activity increases with high cell turnover which is commonly seen in tumors. The aim of this study was to evaluate if sTK1 can be useful as a biomarker to differentiate cats with lymphoma from cats with acute to chronic GI disease. The relation between sTK1 activity and a marker for inflammation, the acute-phase protein serum amyloid A (SAA), was also examined, to evaluate if there is a correlation between sTK1 activity and SAA in cats with GI disease and lymphoma, and if a combination of the two assays strengthens the accuracy and predictive value. Private-owned cats of varying breeds, ages and genders were recruited into three different groups; one group of 41 healthy control cats that were classified as healthy based on clinical examination and blood analysis; one group of 54 cats with GI disease that was presenting with vomiting, diarrhea, weight-loss and/or anorexia and of which a diagnosis related to the GI tract had been reached, and one group of 14 cats with confirmed lymphoma. Sera was collected from all cats and sTK1 activity was measured using the [ 3H]-dThd phosphorylation assay while SAA was measured with a latex turbidimetric immunoassay. The results showed that cats with lymphoma had a significantly higher sTK1 activity compared to both healthy cats (p<0.01) and cats with GI disease (p<0.05), and the sTK1 activity assay for lymphoma had a higher accuracy, sensitivity and specificity compared to the SAA concentration assay for this group. In contrast, the SAA concentration in was significantly higher in cats with GI disease compared to healthy cats (p<0.01) and showed a higher accuracy, sensitivity and specificity compared to the sTK1 activity assay. The combination of sTK1 and SAA analyses showed a small, but statistically significant, added sensitivity and specificity in cats with GI disease, but not in the lymphoma group. There was also a weak correlation between TK1 and SAA in cats with lymphoma and cats with GI disease. This study concludes that sTK1 is not useful as a biomarker for differentiating between lymphoma and GI disease in cats, as there is a high degree of overlap between the two groups. There are however indications that TK1 might be useful in malignancy assessment, monitoring of disease progression and prognosis estimation. Another conclusion is that there is a correlation between TK1 and SAA, although the correlation is weak and the combination of the two values do not strengthen the accuracy or predictive value for cats with lymphoma or GI disease, which means that SAA is not useful as an additional biomarker to sTK1 for this purpose. However, this study indicates that cats with inflammatory disease and pancreatitis may have an elevated sTK1 and SAA in the acute phase of disease that is later decreased if the tissue damage is reduced. More studies with a larger lymphoma group and with follow-up samples for the cats with GI disease and lymphoma are necessary to confirm these conclusions. Further studies on the potential use of both sTK1 and SAA in disease monitoring, malignancy assessment and evaluation of prognosis are also recommended.