The Metabolic Marker Tumour Pyruvate Kinase Type M2 (tumour M2-PK) Shows Increased Expression Along the Metaplasia-dysplasia-adenocarcinoma Sequence in Barrett's Oesophagus

Overview

Journal J Clin Pathol

Specialty Pathology

Date 2004 Oct 29

PMID 15509675

Citations 12

Authors

K Koss

R F Harrison

J Gregory

S J Darnton

M R Anderson

J A Z Jankowski

Affiliations

Soon will be listed here.

Abstract

Background: Proliferating and tumour cells express the glycolytic isoenzyme, pyruvate kinase type M2 (M2-PK). In tumours cells, M2-PK usually exists in dimeric form (tumour M2-PK), causing the accumulation of glycolytic phosphometabolites, which allows cells to invade areas with low oxygen and glucose concentrations.

Aims: To investigate the expression of tumour M2-PK during the metaplasia-dysplasia-adenocarcinoma sequence of Barrett's oesophagus, and to assess the prognostic usefulness of tumour M2-PK in oesophageal cancer.

Materials/methods: One hundred and ninety cases selected from the histopathology archives as follows: 17 reflux oesophagitis, 37 Barrett's oesophagus, 21 high grade dysplasia, 112 adenocarcinomas, and three control tumours. Sections were stained immunohistochemically with antibody to tumour M2-PK.

Results: Tumour M2-PK was expressed in all cases, and increased cytoplasmic expression was seen with progression along the metaplasia-dysplasia-adenocarcinoma sequence. All cases of adenocarcinoma showed 100% staining so that tumour M2-PK was not a useful prognostic marker.

Conclusions: Tumour M2-PK is not a specific marker of Barrett's adenocarcinoma, but may be important as a marker of transformed and highly proliferating clones during progression along the metaplasia-dysplasia-adenocarcinoma sequence.

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References

Ignacak J, Stachurska M . The dual activity of pyruvate kinase type M2 from chromatin extracts of neoplastic cells. Comp Biochem Physiol B Biochem Mol Biol. 2003; 134(3):425-33. DOI: 10.1016/s1096-4959(02)00283-x. View

Hardt P, Toepler M, Ngoumou B, Rupp J, Kloer H . 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(2A):851-3. View

Guindi M, Riddell R . Histology of Barrett's esophagus and dysplasia. Gastrointest Endosc Clin N Am. 2003; 13(2):349-68, viii. DOI: 10.1016/s1052-5157(03)00005-9. View

Schneider J, Schulze G . Comparison of tumor M2-pyruvate kinase (tumor M2-PK), carcinoembryonic antigen (CEA), carbohydrate antigens CA 19-9 and CA 72-4 in the diagnosis of gastrointestinal cancer. Anticancer Res. 2004; 23(6D):5089-93. View

Brinck U, Eigenbrodt E, Oehmke M, Mazurek S, Fischer G . L- and M2-pyruvate kinase expression in renal cell carcinomas and their metastases. Virchows Arch. 1994; 424(2):177-85. DOI: 10.1007/BF00193498. View

Polkowski W, van Lanschot J, Ten Kate F, Baak J, Tytgat G, Obertop H . The value of p53 and Ki67 as markers for tumour progression in the Barrett's dysplasia-carcinoma sequence. Surg Oncol. 1995; 4(3):163-71. DOI: 10.1016/s0960-7404(10)80021-0. View

Eigenbrodt E, Basenau D, Holthusen S, Mazurek S, Fischer G . Quantification of tumor type M2 pyruvate kinase (Tu M2-PK) in human carcinomas. Anticancer Res. 1997; 17(4B):3153-6. View

Bailey T, Biddlestone L, Shepherd N, Barr H, Warner P, Jankowski J . Altered cadherin and catenin complexes in the Barrett's esophagus-dysplasia-adenocarcinoma sequence: correlation with disease progression and dedifferentiation. Am J Pathol. 1998; 152(1):135-44. PMC: 1858126. View

Eigenbrodt E, Kallinowski F, Ott M, Mazurek S, Vaupel P . Pyruvate kinase and the interaction of amino acid and carbohydrate metabolism in solid tumors. Anticancer Res. 1998; 18(5A):3267-74. View

10.

Jankowski J, Wright N, Meltzer S, Triadafilopoulos G, Geboes K, Casson A . Molecular evolution of the metaplasia-dysplasia-adenocarcinoma sequence in the esophagus. Am J Pathol. 1999; 154(4):965-73. PMC: 1866556. DOI: 10.1016/S0002-9440(10)65346-1. View

11.

Shirvani V, Kaur B, Omary M, Triadafilopoulos G . Cyclooxygenase 2 expression in Barrett's esophagus and adenocarcinoma: Ex vivo induction by bile salts and acid exposure. Gastroenterology. 2000; 118(3):487-96. DOI: 10.1016/s0016-5085(00)70254-x. View

12.

El-Omar E, Carrington M, Chow W, McColl K, Bream J, Young H . Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature. 2000; 404(6776):398-402. DOI: 10.1038/35006081. View

13.

Jankowski J, Harrison R, Perry I, Balkwill F, Tselepis C . Barrett's metaplasia. Lancet. 2001; 356(9247):2079-85. DOI: 10.1016/S0140-6736(00)03411-5. View

14.

Schneider J, Morr H, Velcovsky H, Weisse G, Eigenbrodt E . Quantitative detection of tumor M2-pyruvate kinase in plasma of patients with lung cancer in comparison to other lung diseases. Cancer Detect Prev. 2001; 24(6):531-5. View

15.

Schulze G . The tumor marker tumor M2-PK: an application in the diagnosis of gastrointestinal cancer. Anticancer Res. 2001; 20(6D):4961-4. View

16.

Hardt P, Ngoumou B, Rupp J, Kloer H . Tumor M2-pyruvate kinase: a promising tumor marker in the diagnosis of gastro-intestinal cancer. Anticancer Res. 2001; 20(6D):4965-8. View

17.

Mazurek S, Zwerschke W, Jansen-Durr P, Eigenbrodt E . Metabolic cooperation between different oncogenes during cell transformation: interaction between activated ras and HPV-16 E7. Oncogene. 2001; 20(47):6891-8. DOI: 10.1038/sj.onc.1204792. View