M2-PK
Tumour Pyruvate Kinase M2
What it is
Pyruvate kinase M2 (PKM2) is an isoform of the glycolytic enzyme pyruvate kinase that is expressed at high levels in proliferating cells. In most differentiated adult tissues, the tetrameric (active) form of pyruvate kinase predominates, efficiently converting phosphoenolpyruvate to pyruvate and channelling glucose metabolism toward oxidative phosphorylation. In cancer cells and other rapidly dividing cells, the dimeric (M2) form accumulates — and this dimeric form is catalytically less active, causing a metabolic shift that diverts glycolytic intermediates toward biosynthetic pathways (nucleotide synthesis, lipid synthesis, amino acid production) to support rapid cell proliferation. This metabolic reprogramming is part of the Warburg effect. The dimeric M2-PK is shed from proliferating cells into the intestinal lumen and can be detected in stool (stool M2-PK) or in blood (plasma M2-PK). The Blueprint Bloodwork protocol uses stool M2-PK as a complementary colorectal cancer screening marker alongside FIT.
Why we measure it
Stool M2-PK measures a form of the enzyme pyruvate kinase associated with rapidly dividing cells. It complements FIT, which measures blood: some polyps and early cancers bleed intermittently or not at all, so FIT can miss them on any given test. Several studies report stool M2-PK sensitivity for colorectal cancer of about 80–85%, with reasonable specificity, and that combining FIT and M2-PK identifies more adenomas and cancers than FIT alone without substantially increasing false positives. The two measure partly different things — FIT reflects bleeding; M2-PK reflects cell activity. M2-PK is not diagnostic on its own.
Why every 12 months
Annual stool M2-PK testing is appropriate alongside annual FIT. Like FIT, M2-PK is collected from a home stool sample and returned for laboratory analysis. Both tests are coordinated within the Blueprint Bloodwork annual cycle.
What movement means
Stool M2-PK results are typically reported as a quantitative value in Units/mL (U/mL), with a positivity threshold defined by the manufacturer and laboratory. Common positivity thresholds are in the range of 4 U/mL. In published studies, a positive stool M2-PK is followed up in the same way as a positive FIT — with colonoscopy.
Negative
< 4 U/mL (threshold varies by laboratory)
Below the laboratory's positivity threshold. Annual retesting establishes a trend.
Shastri YM et al., Alimentary Pharmacology & Therapeutics, 2006
Positive
≥ 4 U/mL (threshold varies by laboratory)
Above the laboratory's positivity threshold. Research associates raised stool M2-PK with increased cell turnover in the lower gut, which can occur without bleeding and so may be missed by FIT. M2-PK is not diagnostic on its own. Discuss with a registered medical practitioner.
Shastri YM et al., Alimentary Pharmacology & Therapeutics, 2006
This page summarises published research for general education. It is not medical advice and does not interpret individual results. Discuss your results with a registered medical practitioner.
References
- 1.
Shastri YM, Naumann M, Oremek GM, et al.. “Prospective Multicenter Evaluation of Fecal Tumor Pyruvate Kinase Type M2 (M2-PK) as a Screening Biomarker for Colorectal Neoplasia.” International Journal of Cancer. 2006.
- 2.
Hardt PD, Toepler M, Ngoumou B, Rupp J, Kloer HU. “Measurement of Fecal Pyruvate Kinase Type M2 (Tumor M2-PK) Concentrations in Patients with Gastric Cancer, Colorectal Cancer, Colorectal Adenomas and Controls.” Anticancer Research. 2003.
- 3.
Christopoulos C, Kalogeropoulos N. “Pyruvate Kinase M2 as a Biomarker of Colorectal Cancer Screening.” World Journal of Gastrointestinal Oncology. 2019.
- 4.
Vander Heiden MG, Cantley LC, Thompson CB. “Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation.” Science. 2009.