Abstract 5528: Setting the clock: Tumor TK1 is a prognostic marker for disease recurrence
Authors: Alegre Melissa , Germann Brit L. , Leavitt Matthew , Eggett Dennis , Killpack Nathan , Burton Sean , Orton Andrew , Leavitt Cameron , O'Neill Kim L. 
Published: August 2012

Abstract
Cancer is a devastating disease which affects millions of people every year. There is a need for reliable markers which indicate more aggressive tumors. Thymidine kinase 1 (TK1) has been shown to have prognostic potential in the serum of cancer patients, correlating with disease stage and recurrence. Serum TK1 has been studied extensively, but relatively few studies have investigated the prognostic potential of TK1 in tumor tissue. We created a breast array of samples from 300 breast cancer patients with various disease stages and treatment methods. We compared several potential prognostic markers to clinically relevant markers, including TK1, fatty acid synthase (FAS), annexin I, and Ki67. These markers were also compared to tumor progesterone and estrogen receptor status (PR and ER), HER2neu status, type of chemotherapy, and type of hormone therapy. Whether or not the patients received radiation therapy was also considered. Tumors were scored for TK1 staining on a scale from 0 to 2. A TK1 score of 0 indicated that 0-5% of tumor cells stained positive for TK1. A score of 1 or 2 indicated 10%-20% TK1 staining and 20% or more TK1 staining respectively. The relationships between various markers and therapies were analyzed using logistic regression and chi square analysis. Interestingly, tumor TK1 staining did not correlate to tumor stage, and was only moderately correlated to tumor grade. This is different from the results of serum TK1 (sTK1) studies, which have shown correlations between sTK1 and disease stage. Tumor TK1 levels did correlate with Ki67 (p=6.333e-11), but there were no correlations between TK1 and FAS (p=.7927), annexin I (p=.1169), or diagnosis (p=.4303). Markers were also analyzed for their predictive value. Distant metastasis, PR status, and the presence of positive nodes were strong predictors of disease outcome and time to recurrence. If the disease had not metastasized at the time of evaluation, patients were 82.85% more likely to survive. No metastasis also predicted 1.4 years to disease recurrence. Positive PR status also indicated that patients were 4.6 times more likely to die of their disease. Additionally, for every positive node present, patients were 9.8% more likely to die of their disease. The presence of positive nodes also predicted shorter time to disease recurrence by 0.04 years per node. Higher TK1 scores were also found to predict shorter times to recurrence. On the other hand, low TK1 scores were found to be predictive of longer time to recurrence. A score of 2 indicated on average 1.8375 years to disease recurrence. Scores of 0 and 1 indicated 2.8 and 2.4 years on average to recurrence, respectively. Further studies are needed to elucidate the differences between tumor TK1 and sTK1. Additional studies involving larger patient groups may be needed to confirm the relationship between these predictors and recurrence.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5528. doi:1538-7445.AM2012-5528