High thymidine kinase 1 (TK1) expression is a predictor of poor survival in patients with pT1 of lung adenocarcinoma

Department of Pathology, Nanjing Jinling Hospital, Nanjing University Medical School, 305 Zhongshangdong Road, Nanjing, 210002, Jiangsu Province, China.
Tumor Biology (Impact Factor: 3.61). 12/2011; 33(2):475-83. DOI: 10.1007/s13277-011-0276-0
Source: PubMed


In this study, we explore the association of thymidine kinase 1 (TK1) expression in tumour tissues with clinical pathological parameters and prognosis in patients with pathological T1 (pT1) lung adenocarcinoma. The expression of TK1 was studied by immunohistochemistry techniques in 80 patients with surgically resected pT1 lung adenocarcinoma, retrospectively and at >10-year follow-up. Compared to patients with low TK1 expression [labelling index (LI) <25.0%], patients with high TK1 expression (LI ≥ 25.0%) showed significantly increased lymphatic/vascular permeation and lymph node involvement and higher stromal invasion grade and pathological stage, and a greater number of patients had a tumour size of 2.1 to 3.0 cm. The 5-year survival and the mortality during follow-up for patients with high TK1 expression were significantly worse than that of patients with low TK1 expression. The prognoses of the cases with grade 0, grade 1 and grade 2 stromal invasions were similar and were better than those of cases with grade 3. In patients with stromal invasion grade 3, the 5-year survival and the mortality during follow-up were significantly worse for patients with high TK1 compared to patients with low TK1 expression. Univariate analyses showed that stromal invasion and TK1 expression were significant prognostic factors, while in the multivariate analysis, TK1 expression and tumour stage were found to be independent prognostic factors, but not stromal invasion. This is the first study showing that TK1 expression in combination with stromal invasion is a more reliable prognostic factor than stromal invasion classification itself in patients with pT1 lung adenocarcinoma. TK1 expression enables a further classification of the patients and opens opportunities for improved treatment outcome.

16 Reads
  • Source
    • "Immunohistochemical staining was carried out using the EnVision System according to the manufacturer’s instructions (Maxin Biotech, Fuzhou, China), as previously described [12,17]. In brief, two serial sections were used for the staining of human TK1 monoclonal antibody (800 × PBS dilution of 1 mg/ml, SSTK Biotech. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Thymidine kinase 1 (TK1) is a proliferation biomarker that has been found useful for prognostication in cancer patients. Here we investigate for the first time the use of TK1 expression as a prognostic factor for patients with premalignant and malignant lesions of the uterine cervix. Methods TK1 expression was determined by immunohistochemistry in cervical lesions (cervical intraepithelial neoplasia (CIN), n = 216; invasive cervical carcinoma, n = 84). TK1 and Ki-67 expressions and pathological/FIGO stages and age were correlated with 5-year survival by Kaplan-Meier, log rank and COX hazard uni- and multivariate analyses. Results TK1 labeling index (LI) was significantly correlated with CIN grades and invasive cervical carcinoma stages, while TK1 labeling intensity was only correlated to CIN grades. TK1 LI was significantly higher compared with Ki-67 LI. TK1 LI correlated significantly to 5-year survival in patients with invasive cervical carcinoma, particularly nuclear TK1 LI. In a multivariate analysis, nuclear TK1 expression was independent prognostic factor in patients with in situ/invasive cervical carcinoma or in invasive cervical carcinoma alone. Interestingly, in invasive cervical carcinoma patients with advanced tumors, nuclear TK1 expression could identify patients with significantly better survival rates (80%), while Ki-67 could not. Conclusions Nuclear TK1 expression in early grade CIN predicts risk for progression to malignancy. Nuclear TK1 expression is also a prognostic factor for treatment outcome, particularly in patients with advanced cervical carcinomas. Nuclear TK1 expression is more useful than Ki-67 and pathological/FIGO stages.
    Full-text · Article · May 2013 · BMC Cancer
  • [Show abstract] [Hide abstract]
    ABSTRACT: N-Myc downstream-regulated gene 2 (NDRG2) has been demonstrated to influence the metastatic potential of hepatocellular carcinoma and breast cancer cells by regulating CD24 expression. The aim of this study was to investigate the roles of NDRG2 and CD24 in the clinical pathology of lung adenocarcinoma and to explore whether the expression of these two markers can be used as independent factors for the prediction of prognosis in patients with this tumor. NDRG2 and CD24 expression in paraffin-embedded specimens gathered from 166 patients with lung adenocarcinoma was detected by immunohistochemical method. The correlation of these two proteins expression with clinicopathological parameters and prognosis was statistically analyzed. NDRG2 and CD24 proteins were highly expressed in 59/166 (35.5 %) and 110/166 (66.3 %) of lung adenocarcinoma patients, respectively. High expression of NDRG2 was frequently found in lung adenocarcinoma tissues in early pTNM stage (p = 0.01) and without pathological metastasis (p = 0.02), whereas the high expression of CD24 was significantly associated with the advanced pTNM stage (p = 0.04) and pathological metastasis (p = 0.01). Univariate analysis indicated that the patients with NDRG2 high expression correlated with favorable prognosis in patients with lung adenocarcinoma (p = 0.001), as opposed to CD24 (p = 0.001). The survival rate of the patients with NDRG2-low/CD24-high expression was the lowest (p < 0.001). Multivariate statistical analysis showed that the conjoined expressions of NDRG2-high/CD24-low and NDRG2-low/CD24-high were independent prognostic indicators of lung adenocarcinoma (p = 0.03 and p = 0.02, respectively). Our results suggest that the decreased expression of NDRG2 or the increased expression of CD24 is an important feature of lung adenocarcinoma. A combined detection of NDRG2/CD24 co-expression may benefit us in prediction of the prognosis of lung adenocarcinoma.
    No preview · Article · Apr 2012 · Medical Oncology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Tumor-related biomarkers are used for the diagnosis, prognosis and monitoring of treatments and follow-up of cancer patients, although only a few are fully accepted for the detection of invisible/visible tumors in health screening. Thymidine kinase 1 (TK1), a cell cycle-dependent and thus a proliferation-related marker, has been extensively studied during the last decades, using both biochemical and immunological techniques. Therefore, TK1 is an emerging potential proliferating biomarker in oncology that may be used for the prognosis and monitoring of tumor therapy, relapse and survival. In addition, TK1 concentration in serum (STK1p) is a useful biomarker in healthy screening for the detection of potential malignancy development as well as the identification of early-stage tumors, with a few false-positive cases (ROC value, 0.96; tumor proliferation sensitivity, 0.80; specificity, 0.99). In this review, we examine results regarding the expression of STK1p and TK1 in relation to cancer patients and STK1p in health screening published between 2000 and 2012. The use of tumor-related markers recommended by international cancer organizations is also discussed. This review provides valuable information for applications in tumor patients, in health screening and for cancer research.
    Preview · Article · Jan 2013 · Molecular and Clinical Oncology
Show more