Elsevier

Urology

Volume 76, Issue 2, August 2010, Pages 513.e1-513.e6
Urology

Basic and Translational Science
Circulating Tumor M2 Pyruvate Kinase and Thymidine Kinase 1 Are Potential Predictors for Disease Recurrence in Renal Cell Carcinoma After Nephrectomy

https://doi.org/10.1016/j.urology.2010.04.034Get rights and content

Objectives

Pyruvate kinase type M2 (TuM2-PK) and thymidine kinase 1 (TK1) are the key enzymes involved in tumor cells metabolism and proliferation. We explored the association of their preoperative circulating levels with disease recurrence in patients with renal cell carcinoma (RCC).

Methods

We measured the plasma levels of TuM2-PK levels and serum TK1 activity preoperatively in patients with RCC, using a quantitative ELISA, and correlated the results with clinicopathological parameters.

Results

Significantly higher levels of TuM2-PK and TK1 were found in 116 patients with RCC compared with 20 healthy participants (P < .001 and P = .03), but not compared with 27 patients with benign kidney tumors (P = .13 and P = .72). There was a significant association between the level of TuM2-PK and of TK1 activity with T stage (P = .01 and P = .04). Of 2 markers only TuM2-PK was significantly associated with tumor grade (P = .001). The presence of extensive tumor necrosis (> 50%) was associated with high TuM2-PK (P = .001) and low TK1 (P = .03). The 5-year recurrence-free survival for patients with elevated TuM2-PK or TK1 was significantly lower compared with those for patients with normal marker levels (55% vs 94%, P < .001 and 21% vs 90%, P = .002). Multivariate Cox Proportional Hazard analysis demonstrated that TuM2-PK and TK1, adjusted for stage, grade and tumor necrosis were retained as independent predictors of disease recurrence (HR = 7.3, P = .04 and HR = 3.8, P = .03).

Conclusions

The measurements of 2 circulating biomarkers, TuM2-PK and TK1, in RCC patients before nephrectomy can be useful for predicting recurrence and stratifying the patients into risk groups for possible adjuvant treatment.

Section snippets

Study Patients

In this prospective study we included patients with renal masses scheduled for nephrectomy (either radical or nephron-sparing), older than 18 years, with clinical stage T3cN0M0 or less. We also included patients with known metastatic disease who were candidates for cytoreductive surgery with World Health Organization performance status 0-2 and 20 healthy individuals. A total of 163 persons (100 males and 63 females) were found to be eligible. Their characteristics, including histology of the

Results

There was no significant change in the distribution of age and gender between 3 groups: healthy, BKT and RCC (P = .1 and P = .39). Of the 116 patients with RCC, 107 patients had a localized or locally advanced tumor and underwent radical or partial nephrectomy with curative intent. They were followed after surgery for a median of 33 months (range, 1-110 months). The remaining 9 patients had metastatic disease at presentation and underwent cytoreductive nephrectomy. Median follow-up for these

Comment

Tumor cells release into circulation substances that may serve as tumor markers. Although various biomolecules have been tested in RCC none of them as of today appears useful. In this study we estimated the clinical value of 2 circulating biomarkers, TuM2-PK and TK1.

Previous studies have shown that plasma TuM2-PK levels in patients with malignant renal tumors were significantly higher than in healthy donors20 or in patients with benign urological conditions, such as benign prostatic hyperplasia

Conclusions

In conclusion, we found that 2 circulating markers, TuM2-PK and TK1, are capable of predicting disease recurrence in RCC patients after nephrectomy. The use of these 2 markers in combination enhanced the predictive power of testing. The preoperative measurements of TuM2-PK and TK1 may offer valuable prognostic information that can be used in stratification of patients in treatment planning after nephrectomy.

Acknowledgments

We thank Mario Baras of the Hebrew University, Hadassah School of Public Health, for advice on the statistical analysis.

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    B. Nisman and V. Yutkin contributed equally to this work.

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