The tumor metabolic marker Tumor M2-PK in stool: A new biomarker for colorectal cancer

Abstract

3598 Background: Proliferating cells, especially tumor cells, express a special isoenzyme of pyruvate kinase, termed M2-PK which can occur in a tetrameric form with a high affinity to its substrate phosphoenolpyruvate (PEP) and in a dimeric form with a low PEP affinity. In tumor cells the dimeric form is usually predominant and is therefore termed Tumor M2-PK. The dimerisation of M2-PK takes place through direct binding of oncoproteins and leads to decreased enzyme activity as well as the channeling of glucose for the synthesis of nucleic acids, phospholipids and amino-acids. Methods: The present study includes 303 patients that underwent complete colonoscopy after the determination of Tumor M2-PK in a single spot stool sample. Stool samples of patients with colorectal cancer (CRC) and patients without pathological findings were tested. Histology was obtained from the routine biopsies and/or from surgery. Tumor M2-PK in stool extracts was determined immunologically with a quantitative ELISA,which is based on two monoclonal antibodies. Results: Data from 173 controls and 130 patients with CRC have been evaluated. There is a highly significant difference (p < 0.001; Kruskal-Wallis ANOVA test) between tumor patients and controls. At a cut off point of 4 U/ml, the sensitivity was calculated to be 83% for colon cancer and 73% for rectal cancer and the specificity as 82%. Fecal Tumor M2-PK levels of 76 patients with CRC are correlated with tumor staging according to Dukes and TNM classification. Conclusions: The present study shows that the determination of Tumor M2-PK in a single spot stool sample is a valuable tool for the early detection of CRC. No significant financial relationships to disclose.