Abstract

Thymidine Kinase 1 (TK1) is traditionally a serum biomarker which is elevated in the early stages of malignancies. TK1 is a DNA repair enzyme which is typically associated with proliferation. In serum, TK1 is elevated in a stage-like manner and increases as the disease advances. As a well-characterized serum biomarker, relatively little work has been done to establish it as a tumor biomarker. However, tumor TK1 reflects many of the same trends that can be seen with serum TK1. Specifically, tumor TK1 is an early event in tumor progression and increases with grade and stage. This study seeks to demonstrate that, similar to serum TK1, tumor TK1 is a valuable indicator of malignancy in the most common types of cancer in men. In this study we used a highly specific monoclonal antibody to TK1 to histologically stain 10 different types of carcinoma tissue and corresponding normal tissue. We found that TK1 is a good marker for malignancy and is significantly overexpressed in cancers compared to normal controls in lung, colon, prostate, esophagus, stomach, liver, and kidney tissues. Slight differences were found in the staining pattern among various types of lung cancer although virtually all types showed significantly higher TK1 staining compared to normal tissue. Additionally, TK1 expression in prostate carcinoma was significantly higher than from normal tissue, and correlated with an increase in stage. Overall, it is clear that TK1 is a valuable cancer marker in a wide variety of solid tumors and may be considered a universal cancer marker.

Highlights

  • Cancer is the second leading cause of death in the United States but is the number one cause of death in individuals ages 40 to 79 years (Siegel, Naishadham, & Jemal, 2013)

  • Thymidine Kinase 1 (TK1) has been well-characterized as a serum biomarker and similar trends are seen with tumor TK1, this study seeks to compare TK1 expression in a variety of solid tumors

  • TK1 expression was evaluated in 8 different normal tissues from 48 individuals including esophagus, stomach, liver, uterine, colon, rectum, lung, and kidney

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Summary

Introduction

Cancer is the second leading cause of death in the United States but is the number one cause of death in individuals ages 40 to 79 years (Siegel, Naishadham, & Jemal, 2013). The two most prevalent cancer sites which contribute to cancer mortality are lung and prostate Together these account for approximately 38% of cancer deaths in men (Siegel et al, 2013). TK1 is a biomarker which is involved in DNA repair and is upregulated during S phase (He, Skog, & Tribukait, 1991). It is considered a proliferation marker and is often compared with Ki67 and/or proliferating cell nuclear antigen (PCNA). TK1 has been well-characterized as a serum biomarker and similar trends are seen with tumor TK1, this study seeks to compare TK1 expression in a variety of solid tumors.

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