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Annals of Surgical Oncology

Published in:

01-10-2007 | Gastrointestinal Oncology

Current Status of Tumor M2 Pyruvate Kinase (Tumor M2-PK) as a Biomarker of Gastrointestinal Malignancy

Authors: Harsha R. Hathurusinghe, MRCS, Kolitha S. Goonetilleke, MRCS, Ajith K. Siriwardena, MD FRCS

Published in: Annals of Surgical Oncology | Issue 10/2007

Abstract

Background

Tumor pyruvate kinase M2 (tumor M2-PK) is a key enzyme in the altered metabolism of tumor tissue. In cancer, it is known to be present in high concentrations in malignant tissue, plasma and other body fluids. A commercial enzyme-linked immunosorbent assay (ELISA) method exists for the detection of tumor M2-PK. This study undertakes a systematic review of the current literature on tumor M2-PK as a diagnostic tool and provides an overview of the current usage and scope of this emerging biomarker.

Methods

The MEDINE and EMBASE databases were searched for English-language articles containing original data. MeSH headings used were pyruvate kinase, tumor and cancer. All case reports and review articles were excluded and a final study population of 30 manuscripts containing original data was obtained.

Results

Eight articles evaluated plasma tumor M2-PK in 511 esophago-gastric cancer, 226 pancreatobiliary cancer and 470 colorectal cancer patients. Although there are inter-study variations in cut-off points, consistent findings include elevated levels in patients with malignancy with the degree of elevation corresponding to extent of disease.

Conclusion

Tumor M2-PK is elevated in a range of gastrointestinal malignancy. In pancreatobiliary malignancy, the weight of evidence suggests that the test can be used as an adjunctive diagnostic test in conjunction with CA 19-9 and also that it may be a valuable biomarker of adverse prognosis. Stool tumor M2-PK appears to be a promising test for colon cancer.

Eigenbrodt E, Basenau D, Holthusen S, et al. Quantification of tumor type M2 pyruvate kinase (Tu M2-PK) in human carcinomas. Anticancer Res 1997;17:3153–6PubMed

Schneider J, Morr H, Velcovsky HG, et al. Quantitative detection of tumor M2-pyruvate kinase in plasma of patients with lung cancer in comparison to other lung diseases. Cancer Detect Prev 2000;24:531–5PubMed

Eigenbrodt E, Kallinowski F, Ott M, et al. Pyruvate kinase and the interaction of amino acid and carbohydrate metabolism in solid tumors. Anticancer Res 1998;18:3267–74PubMed

Mazurek S, Eigenbrodt E. The tumour metabolome. Anticancer Res 2003;23:1149–54PubMed

Brinck U, Eigenbrodt E, Oehmke M, et al. L- and M2-pyruvate kinase expression in renal cell carcinomas and their metastases. Virchows Arch 1994;424:177–85PubMedCrossRef

Warburg O, Gawehn K, Geissler AW, et al. Experiments on anaerobiosis of cancer cells. Klin Wochenschr 1965;15:289–93 [article in German]CrossRef

Eigenbrodt E, Leib S, Kramer W, Friis RR, Schoner W Structural and kinetic differences between the M2 type pyruvate kinases from lung and various tumors. Biomed Biochim Acta 1983;42:S278–82PubMed

Taketa K, Shimamura J, Ueda M, Shimada Y, Kosaka K Profiles of carbohydrate-metabolizing enzymes in human hepatocellular carcinomas and preneoplastic livers. Cancer Res 1988;48:467–74PubMed

Guderley H, Fournier P, Auclair JC Phylogeny congruence analysis and isozyme classification: the pyruvate kinase system. J Theor Biol 1989;140:205–20PubMed

10.

Newsholme EA, Board M Application of metabolic-control logic to fuel utilization and its significance in tumor cells. Adv Enzyme Regul 1991;31:225–46PubMedCrossRef

11.

Presek P, Reinacher M, Eigenbrodt E Pyruvate kinase type M2 is phosphorylated at tyrosine residues in cells transformed by Rous sarcoma virus. FEBS letters 1988;242:194–98PubMedCrossRef

12.

Zwerschke W, Mazurek S, Eigenbrodt, et al. Modulation of type M2 pyruvate kinase activity by the human papillomavirus type 16 E7 oncoprotein. Proc Natl Acad Sci USA 1999;96:1291–6

13.

Mazurek S, Michel A, Eigenbrodt E Effect of extracellular AMP on cell proliferation and metabolism of breast cancer cell lines with high and low glycolytic rates. J Biol Chem 1997;272:4941–52PubMedCrossRef

14.

Eigenbrodt E, Reinacher M, Scheefers, Borchel U, Scheefers H, Friis R. Double role for pyruvate kinase type M2 in the expansion of phosphometabolite pools found in tumor cells. Critical reviews in oncogenesis. Crit Rev Oncog 1992;3:91–115

15.

Mazurek S, Boschek C, Hugo F, et al. Pyruvate kinase type M2 and it’s role in tumour growth and spreading. Semin Cancer Biol 2005;15:300–8PubMedCrossRef

16.

Hacker HJ, Steinberg P, Bannasch P, et al. Pyruvate kinase isoenzyme shift from L-type to M2-type is a late event in the hepatocarcinogenesis induced in rats by a choline-deficient/DL-ethionine-supplemented diet. Carcinogenesis 1998;19:99–107PubMedCrossRef

17.

Mazurek S, Grimm H, Oehmke M, et al. Tumor M2-PK and glutaminolytic enzymes in the metabolic shift of tumor cells. Anticancer Res 2000;20:5151–4PubMed

18.

Koss K, Harrison RF, Gregory J, et al. The metabolic marker tumor pyruvate kinase type M2 (tumor M2-PK) shows increased expression along the metaplasia-dysplasia-adenocarcinoma sequence in Barrett’s oesophagus. J Clin Pathol 2004;57:1156–9PubMedCrossRef

19.

Oremek GM, Teigelkamp S, Kramer W, et al. The pyruvate kinase isoenzyme tumor M2 (Tu-M2-PK) as a tumor marker for renal carcinoma. Anticancer Res 1999;19:2599–601PubMed

20.

Hugo F, Fischer G, Eigenbrodt E Quantitative detection of tumor M2-PK in serum and plasma. Anticancer Res 1999;19:2753–7PubMed

21.

Oremek GM, Gerstmeier F, Sauer Eppel H, Sapoutzis N, Wechsel HW Pre-analytical problems in the measurement of tumor type pyruvate kinase tumor M2-PK. Anticancer Res 2003;23:1127–30PubMed

22.

Oremek GM, Eigenbrodt E, Radle J, et al. Value of the serum levels of the tumour marker Tu-M2-PK in pancreatic cancer. Anticancer Res 1997;17:3031–4PubMed

23.

Hardt PD, Ngoumou BK, Rupp J, Schnell-Kretschmer H, Kloer HU Tumour M2-pyruvate kinase: A promising tumor marker in the diagnosis of gastro-intestinal cancer. Anticancer Res 2000;20:4965–8PubMed

24.

Schulze G The tumor Marker Tumor M2-PK: An application in the diagnosis of gastrointestinal cancer. Anticancer Res 2000;20:4961–4PubMed

25.

Schneider J, Schulze G Comparison of tumor M2-pyruvate kinase, carcinoembryonic antigen, carbohydrate antigens CA 19-9 and CA 72-4 in the diagnosis of gastrointestinal cancer. Anticancer Res 2003;23:5089–94PubMed

26.

Zhang B, Chen J, Chen D, Wang G, Shen P Tumor type M2 pyruvate kinase expression in gastric cancer, colorectal cancer and controls. World J Gastrenterol 2004;10:1643–6

27.

Schneider J, Bitterlich N, Schulze G Improved sensitivity in the diagnosis of gastro-intestinal tumors by fuzzy logic-based tumor marker profiles including the tumor M2-PK. Anticancer Res 2005;25:1507–16PubMed

28.

Ventrucci M, Cipolla A, Racchini C, et al. Tumor M2-pyruvate kinase, a new metabolic marker for pancreatic cancer. Dig Dis Sci 2004;49:1149–55PubMedCrossRef

29.

Cherwenka H, Aigner R, Bacher H, et al. TUM2-PK (Pyruvate kinase type tumor M2), CA 19-9 and CEA in patients with benign, Malignant and metastasizing pancreatic lesions. Anticancer Res 1999;19:849–52

30.

Goonetilleke KS, Mason JM, Siriwardana P, et al. Diagnostic and prognostic value of plasma tumor M2 pyruvate kinase in periampullary cancer. Evidence for a novel biological marker of adverse prognosis. Pancreas 2007;34:318–24PubMedCrossRef

31.

Hardt P, 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 Res 2003;23:851–4PubMed

32.

Hartd P, Mazurek S, Toepler M, et al. Fecal tumor M2 Pyruvate kinase : A new sensitive screening tool for colorectal cancer. Br J Cancer. 2004;91:980–4

33.

Tonus C, Neupert G, Sellinger M. Colorectal cancer screening by non-invasive metabolic biomarker fecal tumor M2-PK. World J Gastroenterol 2006;12:7007–11PubMed

34.

Oremek GM, Rutner F, Sapoutzis N, et al. Tumor marker pyruvate kinase type m2 in patients suffering from Diabetic Nephropathy. Anticancer Res 2003;23:1155–8PubMed

35.

Oremek GM, Muller R, Sapoutzis N, et al. Tumor marker pyruvate kinase type tumor M2 plasma levels in patients afflicted with Rheumatic diseases. Anticancer Res 2003;23:1131–4PubMed

36.

McDowell G, Gupta S, Dellerba M, et al. Plasma concentrations of tumour dimeric pyruvate kinase are increased in patients with chronic cardiac failure. Ann Clin Biochem 2004;41:491–3PubMedCrossRef

37.

Staib P, Hoffmann M, Schinkothe T. Plasma levels of tumor M2-pyruvate kinase should not be used as a tumor marker for hematological malignancies and solid tumors. Clin Chem Lab Med 2006;44:28–31PubMedCrossRef

38.

Paganuzzi M, Onetto M, Marroni P, et al. CA 19-9 and CA 50 in benign and malignant pancreatic and biliary diseases. Cancer 1988;61:2100–8PubMedCrossRef

39.

Goonetilleke KS, Siriwardena AK. Systematic review of carbohydrate antigen (CA 19-9) as a biochemical marker in the diagnosis of pancreatic cancer. Eur J Surg Oncol 2006 [Epub ahead of print]

40.

Steeg PS Tumor metastasis: mechanistic insights and clinical challenges. Nat Med 2006;12:895–904PubMedCrossRef

41.

Papadopooulos N, Kinzler KW, Vogelstein B The role of companion diagnostics in the development and use of mutation-targeted cancer therapies. Nat Biotechnol 2006;24:985–95CrossRef

42.

Jhala N, Jhala D, Vickers SM, et al. Biomarkers in diagnosis of pancreatic carcinoma in fine-needle aspirates. Am J Clin Pathol 2006;126:572–9PubMed

43.

Gronborg M, Kristiansen TZ, Iwahori A, et al. Biomarker discovery from pancreatic cancer secretome using a differential proteomic approach. Mol Cell Proteomics 2006;5:157–72PubMedCrossRef

44.

Prasad NB, Biankin AV, Fukushima N, et al. Gene expression profiles in pancreatic intraepithelial neoplasia reflect the effects of Hedgehog signaling on pancreatic ductal epithelial cells. Cancer Res 2005;65:1619–26PubMedCrossRef

Title: Current Status of Tumor M2 Pyruvate Kinase (Tumor M2-PK) as a Biomarker of Gastrointestinal Malignancy
Authors: Harsha R. Hathurusinghe, MRCS
Kolitha S. Goonetilleke, MRCS
Ajith K. Siriwardena, MD FRCS
Publication date: 01-10-2007
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue 10/2007
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-007-9481-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Current Status of Tumor M2 Pyruvate Kinase (Tumor M2-PK) as a Biomarker of Gastrointestinal Malignancy

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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