Thymidine Kinase as a Proliferative Marker: Clinical Relevance in 1,692 Primary Breast Cancer Patients

Broët, Philippe; Romain, Sylvie; Daver, A; Ricolleau, G.; Quillien, Véronique; Rallet, A.; Asselain, Bernard; Martin, Pierre Marie; Spyratos, Frédérique

doi:10.1200/jco.2001.19.11.2778

Cited by 79 publications

(54 citation statements)

References 34 publications

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“…TK activity was also determined in cytosol fractions of breast tumor tissues of 1,692 patients. High TK1 activity correlated to a shorter survival, as well as poor outcome of chemotherapy and endocrine treatment (tamoxifen) (23). Cytosolic TK activity also correlated with tumor stage and grade in primary bladder carcinomas (24).…”

Section: Discussionmentioning

confidence: 92%

“…The concentration of TK1 in serum (STK1), rather than its activity, was also found to be a useful marker in monitoring the outcome of tumor therapy in patients with breast (21), gastric (22), and lung (40) cancer. TK1 may also be used as a molecular therapeutic target (23). In primary bladder carcinomas, cytosolic TK activity in T1 tumors was twice that of Ta tumors.…”

Section: Introductionmentioning

confidence: 99%

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Thymidine kinase 1: A proliferation marker for determining prognosis and monitoring the surgical outcome of primary bladder carcinoma patients

Zhang

Quan-an²,

Zou³

et al. 2006

Oncol Rep

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Abstract. Reliable markers for monitoring bladder tumor therapy are needed to evaluate treatment effectiveness. Thymidine kinase 1 (TK1) is an enzyme involved in DNA synthesis and therefore proliferation-dependent. Serum concentration of TK1 (STK1) correlates with malignancy in various types of cancer, thus reflecting treatment results. This study explores for the first time the use of STK1 concentration, both as a prognostic marker and to monitor the outcome of bladder carcinoma surgery. STK1 in 56 bladder carcinoma patients was measured pre-operatively, and postoperatively at 1 week and 1, 3, and 6 months, using an immune ECL dot blot assay. An anti-TK1 chicken IgY antibody was used to determine STK1 concentrations. Mean pre-operative STK1 of bladder carcinoma patients was significantly higher than that of healthy individuals, with no overlap of individual values. STK1 concentrations increased significantly with tumor stage (I-III) and T-values (T1-T2), but not tumor grade (G1-G4). STK1 gradually declined, being 66% lower after 1 week. STK1 reached the level of healthy controls at 1 month and remained there for at least 6 months, post-operatively until this study ended. Since STK1 concentration correlates with tumor stage, degree of invasion and metastasis, and monitors the surgical outcome, it can be a reliable index to diagnose and determine prognosis in post-operative bladder carcinoma.

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Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Thymidine kinase 1: A proliferation marker for determining prognosis and monitoring the surgical outcome of primary bladder carcinoma patients

Zhang

Quan-an²,

Zou³

et al. 2006

Oncol Rep

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“…It is of considerable interest in clinical settings because its level is highly dependent on cell growth. TK1 is a sensitive and specific marker for prognosis (16,18,19), for the monitoring of the outcome of cancer therapy (25)(26)(27)(28), and for the screening of healthy individuals for the risk of malignant disease (unpublished data).…”

Section: Discussionmentioning

confidence: 99%

“…It is almost undetectable in normal serum (14)(15)(16), but increases to varying degrees in malignant tumors, depending on their type, stage (16), whether they are fast or slow growing (17), and whether they are treated or untreated (18). In a clinical study of 1,692 breast cancer patients (19), TK1 activity in the cytosol was correlated to a shorter survival time and poor outcome using endocrine treatment (tamoxifen) (20). Furthermore, commercially available anti-TK1 antibodies have recently provided an attractive alternative in clinical cancer applications.…”

Section: Introductionmentioning

confidence: 99%

Serum thymidine kinase 1 reflects the progression of pre-malignant and malignant tumors during therapy

Zhang²,

Shu³

et al. 2008

Mol Med Rep

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Abstract. This study evaluated the clinical utility of serum thymidine kinase 1 (STK1) in following the progression of pre-malignancies and malignancies and in monitoring the response of common carcinomas to therapy within a routine clinical setting. The STK1 concentration levels of patients with malignancies (n=224), pre-malignancies (n=10), non-tumor/ non-proliferating diseases (systemic lupus erythematosus, SLE) (n=53), benign tumors (n=20) and healthy volunteers (n=761) were determined by enhanced chemoluminescence dot blot assay. Prior to treatment, STK1 levels in the pre-malignant group alone (3.1±2.3) or in the pre-malignant and malignant groups together (2.3±1.9) were significantly higher than in the benign (1.4±0.8), SLE (1.1±0.8) or healthy volunteer (0.6±0.4) groups (p<0.01). According to ROC analysis, the STK1 assay provided a high degree of discrimination between STK1-positive pre-malignant (0.978) or pre-malignant + malignant (0.941) patients and STK1-negative healthy individuals. After varying treatments (surgery, chemotherapy, X-ray), STK1 levels increased by 40-50% during the first month, then decreased back to normal values or even lower. Following treatment, STK1 levels were significantly increased in squamous cell carcinoma (SCC) as compared to adenocarcinoma (AC) patients. In other types of malignancies, STK1 levels decreased from as early as the first month. The STK1 levels of relapsed treated patients were significantly higher (50-60%) than those of mid/long-term treated patients. In conclusion, the STK1 assay discriminated between patients with malignancies and healthy individuals very well, and is therefore potentially useful for a broad range of clinical applications. For example, it could be used for the evaluation of early tumor progression or of tumor progression during therapy in routine clinical settings, as well as for the screening of healthy individuals.

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“…This assay can provide prognostic information in malignancies, and in some cases can aid in the choice of therapy (15)(16)(17)(18)(19)(20)(21)(22). The assay has disadvantages in that it uses 125 I, is relatively complex, and partly measures the activity of TK2.…”

confidence: 99%

Sensitive Nonradiometric Method for Determining Thymidine Kinase 1 Activity

Öhrvik¹,

Lindh²,

Einarsson³

et al. 2004

Clinical Chemistry

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Thymidine Kinase as a Proliferative Marker: Clinical Relevance in 1,692 Primary Breast Cancer Patients

Cited by 79 publications

References 34 publications

Thymidine kinase 1: A proliferation marker for determining prognosis and monitoring the surgical outcome of primary bladder carcinoma patients

Thymidine kinase 1: A proliferation marker for determining prognosis and monitoring the surgical outcome of primary bladder carcinoma patients

Serum thymidine kinase 1 reflects the progression of pre-malignant and malignant tumors during therapy

Sensitive Nonradiometric Method for Determining Thymidine Kinase 1 Activity

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