ORIGINAL ARTICLE Fecal Dimeric M2-Pyruvate Kinase (Tumor M2-PK) in the Differential Diagnosis of Functional and Organic Bowel Disorders Jinny Jeffery, DPhil,* Stephen J. Lewis, FRCP, † and Ruth M. Ayling, FRCPath* Background: Fecal inflammatory markers have been shown to be useful as noninvasive screening tools to differentiate patients with functional from organic bowel pathology. Of these markers calprotectin has been the most intensively studied. More recently, the dimeric isoform of M2-pyruvate kinase (tumor M2-PK) has been suggested as a marker of gastrointestinal inflammation. The aim of this study was to investigate fecal tumor M2-PK in the dif- ferentiation of functional from organic bowel disease. Methods: Fecal calprotectin and tumor M2-PK were measured in 94 controls and 105 gastroenterology outpatients with a possi- ble diagnosis of organic bowel disease. The diagnosis was made by clinical, endoscopic, and radiological criteria. Results: Organic bowel disease was diagnosed in 14 patients (13%). Median calprotectin and tumor M2-PK concentrations were 24.5 lg/g and 1 U/mL in controls, 23 lg/g and 1 U/mL in functional, and 227.5 lg/g and 12.6 U/mL in organic bowel dis- ease. Sensitivity, specificity, and positive and negative likelihood ratios for diagnosis of organic bowel disease were 93%, 92%, 11.6, and 0.07 for calprotectin and 67%, 88% 5.6, and 0.18 for tu- mor M2-PK, respectively. Calprotectin in combination with tumor M2-PK gave a sensitivity of 64%, specificity of 98%, and likeli- hood ratios of 32 and 0.03. Elevated calprotectin or tumor M2-PK decreased specificity to 87%, but increased sensitivity to 100%. Conclusions: Tumor M2-PK is able to differentiate organic from functional bowel disease but has a lower sensitivity, speci- ficity, and predictive value than calprotectin. Further studies are required, alone or in combination with other markers, before its usefulness in this setting can be recommended. (Inflamm Bowel Dis 2009;15:1630–1634) Key Words: inflammatory bowel disease, Crohn’s disease, calprotectin, tumor M2-PK T he differentiation of organic from functional bowel dis- orders is a significant issue in gastroenterology. The use of fecal inflammatory markers in diagnosis has been a focus of attention recently, particularly as such tests are noninvasive and comparatively easy and cheap to perform. Pyruvate kinase is the enzyme that catalyzes the last reaction of the glycolytic pathway from phosphoenolpyruvate to lactate. A number of isoforms of pyruvate kinase exist and their expression is related to the metabolic activity of the tissue concerned. M2-pyruvate kinase (M2-PK) is found in undifferentiated tissues and cells with rapid turnover and can oscillate between tetrameric and dimeric forms. 1 The dimeric form, often referred to as tumor M2-PK, is commonly expressed in cancer cells and can be detected in plasma. It has been found to be elevated in patients with many cancers including those of the gastrointestinal tract, 2 lung, 3 breast, 4 and kidney. 5 Plasma M2-PK has been noted to be elevated in inflammatory conditions such as rheumatoid arthritis. 6 Fecal tumor M2-PK has been investigated as a biomarker in color- ectal malignancy 7–9 with a sensitivity of 91% for colorectal cancer and 60% for polyps >10 mm and specificity of 92%. 9 Calprotectin, another protein whose fecal concentra- tion has been investigated as a diagnostic tool in colorectal cancer, was found to have a sensitivity and specificity for colorectal cancer and polyps of 79% and 72%, respec- tively. 10 However, calprotectin has been more extensively studied as a marker of gastrointestinal inflammation. Its concentration has been shown to be elevated in adults 11,12 and children 13 with inflammatory bowel disease (IBD) and to be of use in distinguishing functional from organic bowel disease 12 and predicting relapse in IBD. 14 Recent studies of fecal tumor M2-PK have suggested that it has potential as a marker of intestinal inflammation in adults 15 and of IBD activity in children. 16 The aim of this study was therefore to investigate measurement of fecal M2- PK in the differentiation of functional and organic bowel disorders. MATERIALS AND METHODS Patients Participants in the study were 105 patients (62 female) attending the Gastroenterology Out Patients Department of a Received for publication February 3, 2009; Accepted February 26, 2009. From the *Department of Clinical Biochemistry, and † Department of Gastroenterology, Derriford Hospital, Plymouth, PL6 8DH UK. Reprints: Dr. Ruth M. Ayling, FRCPath, Department of Gastroenterology, Derriford Hospital, Plymouth, PL6 8DH UK (e-mail: ruthayling@ clinicalbiochemistry.org.uk) Copyright V C 2009 Crohn’s & Colitis Foundation of America, Inc. DOI 10.1002/ibd.20946 Published online 21 May 2009 in Wiley InterScience (www.interscience. wiley.com). Inflamm Bowel Dis  Volume 15, Number 11, November 2009 1630 Downloaded from https://academic.oup.com/ibdjournal/article/15/11/1630/4643432 by guest on 29 November 2023