Thymidine kinase 1 expression in atypical ductal hyperplasia significantly differs from usual ductal hyperplasia and ductal carcinoma in situ: A useful tool in tumor therapy management

Abstract

Thymidine kinase 1 (TK1) is an enzyme involved in the synthesis of DNA precursors. In studies using immunohistochemistry, it was reported to be a more useful proliferation marker than Ki-67 and PCNA in breast, lung and colorectal carcinoma. In this study, we extend the work of prior breast carcinoma studies by investigating the expression of TK1 in 132 patients with usual ductal hyperplasia (UDH), atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). TK1 and Ki-67 expression were determined with monoclonal antibodies using the SP technique. The expression of TK1 was found to be significantly increased in the breast ductal carcinomas in the following manner: UDH<ADH<DCIS<IDC. TK1 expression was correlated with histological grade in DCIS and IDC patients and with pathological stage in IDC patients. The degree of TK1-positive staining in the tumors of patients with ADH, DCIS and IDC was 80-90%, while the corresponding value for UDH patients was less than 5%. TK1 and Ki-67 expression showed very high correlation in the four tumor groups investigated. Since the expression of TK1 varied significantly between the breast ductal subgroups, we concluded that TK1 is a reliable proliferation marker for the determination of breast tumor proliferation, particularly of pre-cancerous lesions (ADH). This may enable timely treatment in the early stages of tumor development using minimal access surgery, thus avoiding extensive radical breast surgery and improving survival rates and the quality of life.