The M2 isoenzyme of pyruvate kinase (M2-PK) is specifically expressed in tumor cells (TU M2-PK) and may therefore provide a tumor marker for malignancies. We have investigated the plasma concentrations of TU M2-PK in patients with renal cell carcinoma (RCC), transitional cell carcinoma of the bladder (BCA), prostate cancer (PCA) and benign prostatic hyperplasia (BPH). TU M2-PK was quantified with a commercially available enzyme-linked immunosorbent assay (ELISA) kit. Using this ELISA kit, plasma samples of 57 healthy individuals were compared to 63 patients with RCC, 36 patients with BCA, 58 patients with PCA and 28 patients with BPH. Patients with carcinomas were subdivided into those patients with nonmetastatic and those with metastatic disease. Only patients with RCC (nonmetastatic and metastatic) showed significantly increased concentrations of TU M2-PK compared to normal individuals. In metastatic RCC, TU M2-PK levels were highest and were also significantly enhanced compared to nonmetastatic RCC. The sensitivity for nonmetastatic RCC was 27.5% and for metastatic RCC 66.7% at the 95% reference value of the control group. In BCA, PCA and BPH, no significant differences could be detected. Our results indicate that TU M2-PK concentrations in plasma may be a potential biomarker of advanced RCC.

Tumor cell metabolism is characterized by a high rate of aerobic glycolysis. The metabolic differences require changes in glycolytic enzyme activities and isoenzyme patterns. The inactive form of the M2 pyruvate kinase (Tu M2-PK) is specifically expressed in tumor cells and has been detected immunohistochemically in tumor tissue but also in peripheral blood of patients with different malignant tumors. In this study, Tu M2-PK in the plasma of patients with renal cell carcinoma (RCC) was compared with healthy volunteers. Tu M2-PK was quantified with a commercially available enzyme linked immunosorbent assay (ELISA) kit. Using the ELISA kit, plasma probes of 57 healthy individuals were compared to 63 patients with RCC (51 patients with non-metastatic RCC, 12 patients with metastatic RCC). Statistical analysis was performed with the non-parametric ANOVA test according to Kruskal-Wallis. In patients with renal cell carcinoma, Tu M2-PK was significantly higher than in healthy volunteers. For organ-defined, non-metastatic tumors, sensitivity was only 27.5%, if the 95% reference values of the control group were used for discrimination. The differences were more pronounced in patients with metastatic disease. Tu M2-PK was significantly enhanced compared to healthy controls, but also to the group with non-metastatic disease, the sensitivity was 66.7%. Our data show that Tu M2-PK has no impact as an unspecific marker for the diagnosis of renal cell carcinoma. This is especially relevant to organ-defined, non-metastatic RCC. In advanced metastatic disease, a potential importance as a parameter for treatment control in palliative therapeutic approaches can be assumed, and warrants further investigations.