Abstract
Proliferating cells express the pyruvate kinase isoenzyme type M2 (M2‐PK). This enzyme exists as an active tetramer and an inactive dimer. The dimeric form is predominantly found in tumor cells and is therefore termed Tumor M2‐PK (TuM2‐PK). TuM2‐PK molecules are released into the peripheral blood and may hereby function as a marker of tumor load in cancer patients. Our study was aimed to investigate TuM2‐PK as a potential plasma marker in melanoma patients compared to the well‐established serum marker S100β. We measured the concentration of TuM2‐PK in plasma and S100β in corresponding serum samples from 300 melanoma patients and 53 healthy controls using a sandwich ELISA and an immunoluminometric assay, respectively. Plasma concentrations of TuM2‐PK were significantly increased in melanoma patients compared to healthy controls (9.30 U/ml vs. 7.20 U/ml; p = 0.0036) and correlated with tumor load (p < 0.0005) and disease stage (p < 0.0005). Patients with elevated plasma TuM2‐PK (cut‐off = 15 U/ml) presented a reduced overall (p < 0.000005) and progression‐free (p = 0.023) survival. Multivariate analysis revealed plasma TuM2‐PK and serum S100β as independent predictors of overall survival in metastasized patients. Neither plasma TuM2‐PK nor serum S100β showed prognostic relevance for tumor‐free patients. Although the sensitivity and specificity to predict disease progression or death was higher for serum S100β compared to plasma TuM2‐PK, the combination of both markers improved the estimation of prognosis compared to that of serum S100β alone. © 2005 Wiley‐Liss, Inc.