PROGNOSTIC VALUE OF CYTOSOLIC THYMIDINE KINASE-ACTIVITY AS A MARKER OF PROLIFERATION IN BREAST-CANCER

Thymidine kinase (TK) is involved in DNA synthesis by the salvage path way. In this study, thymidine kinase (TK) was determined in routinely prepared cytosols of primary tumors from 290 breast-cancer patients. E nzyme activity was measured using a radioenzymatic method optimized fo r detection of the fetal isoenzyme. High levels of TK (greater than or equal to 126 mU/mg protein) were positively associated with histologi cal grade in both pre/peri- and post-menopausal patients. In pre/peri- menopausal patients, high concentrations of TK were also found move fr equently in progesterone receptor (PgR)-negative tumors than in PgR-po sitive samples. In post-menopausal patients, high levels of TK were as sociated with large tumor size, estrogen receptor (ER) negativity and PgR negativity. In univariate analysis, high levels of TK were strongl y associated with shorter overall survival in both pre/peri- (p = 0.00 1) and postmenopausal patients (p = 0.02). pre/peri-menopausal patient s whose tumors had high levels of TK also had an increased risk of rel apse (p = 0.001), In multivariate analysis (including treatment protoc ol, patient age, lymph-node involvement, tumor size, histological grad e, ER and PgR status), TK status was found to be an independent progno stic factor for recurrence-free survival in pre/peri-menopausal patien ts with a weight similar to that of PgR status. In post-menopausal pat ients, TK was the only factor selected for overall survival. (C) 1995 Wiley-Liss, Inc.