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Open Access 01-12-2009 | Research article

Complete absence of M2-pyruvate kinase expression in benign pancreatic ductal epithelium and pancreaticobiliary and duodenal neoplasia

Authors: Mark M Aloysius, Abed M Zaitoun, Timothy E Bates, Abdulkader Albasri, Mohammad Ilyas, Brian J Rowlands, Dileep N Lobo

Published in: BMC Cancer | Issue 1/2009

Abstract

Background

Elevated serum concentrations of M2-pyruvate kinase (M2-PK) correlate with poor prognosis in patients with pancreaticobiliary and duodenal cancer, but the expression of M2-PK in formalin-fixed pancreatic tissue is unknown. We aimed to characterise the immunohistochemical expression of M2-PK in archived specimens of pancreaticobiliary and duodenal cancers, premalignant lesions, chronic pancreatitis, and normal pancreas.

Methods

Immunohistochemical staining was performed with mouse anti-M2-PK monoclonal antibody (clone DF-4) at an optimal dilution of 1:25 on tissue microarrays constructed from formalin-fixed paraffin-embedded pancreatic tissue of 126 consecutive patients undergoing pancreatic resections between June 2001 and June 2006. 104 underwent resection for cancer and 22 for chronic pancreatitis. 78 specimens of chronic pancreatitis tissue were obtained adjacent to areas of cancer. Normal pancreatic tissue was obtained from the resection specimens in a total of 30 patients. Metastatic tumours in 61 regional lymph nodes from 61 patients were also studied. A further 11 premalignant pancreaticobiliary and duodenal lesions were studied. M2-PK expression was quantified with the immunohistochemical score (IHS; Range 0-12).

Results

Benign non-ductal tissue in chronic pancreatitis and normal pancreas showed variable expression of M2-PK (IHS = 1 in 25%, IHS = 2-3 in 40%, IHS>3 in 40%). Benign pancreatic ductal epithelium, all primary pancreaticobiliary and duodenal premalignant lesions and cancers (and lymph node metastasis) showed complete lack of expression (IHS = 0).

Conclusion

Complete lack of M2-PK expression was observed in benign pancreatic ducts, premalignant lesions and cancer. M2-PK is present only in benign non-ductal epithelium in normal pancreas and peri-tumoural tissue.

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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: 3153-3156.PubMed

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: 3267-3274.PubMed

Schneider J, Morr H, Velcovsky HG, 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. 2000, 24: 531-535.PubMed

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: 6891-6898. 10.1038/sj.onc.1204792.CrossRefPubMed

Mazurek S, Boschek CB, Eigenbrodt E: The role of phosphometabolites in cell proliferation, energy metabolism, and tumor therapy. J Bioenerg Biomembr. 1997, 29: 315-330. 10.1023/A:1022490512705.CrossRefPubMed

Mazurek S, Eigenbrodt E: The tumor metabolome. Anticancer Res. 2003, 23: 1149-1154.PubMed

Brinck U, Eigenbrodt E, Oehmke M, Mazurek S, Fischer G: L- and M2-pyruvate kinase expression in renal cell carcinomas and their metastases. Virch Archiv. 1994, 424: 177-185.CrossRef

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 Res. 2003, 23: 851-853.PubMed

Schulze G: The tumor marker tumor M2-PK: an application in the diagnosis of gastrointestinal cancer. Anticancer Res. 2000, 20: 4961-4964.PubMed

10.

Goonetilleke KS, Mason JM, Siriwardana P, King NK, France MW, Siriwardena AK: 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: 318-324. 10.1097/MPA.0b013e31802ee9c7.CrossRefPubMed

11.

Mottet N, Dumollard J-M, Gouzy-Grosjean F, Lucht-Versini P, Péoch M, Thibaudeau E, Rivière M: Expression profiling of M2PK in 19 different human tumor types. AACR Meeting Abstracts, April 2007. 2007, 176-(accessed 1 June 2009), [http://www.aacrmeetingabstracts.org/cgi/content/meeting_abstract/2007/1_Annual_Meeting/176?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=1&author1=Mottet%2C+N&andorexacttitle=and&andorexacttitleabs=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&fdate=1/1/2004&tdate=12/31/2008&resourcetype=HWCIT]

12.

Kononen J, Bubendorf L, Kallioniemi A, Barlund M, Schraml P, Leighton S, Torhorst J, Mihatsch MJ, Sauter G, Kallioniemi OP: Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med. 1998, 4: 844-847. 10.1038/nm0798-844.CrossRefPubMed

13.

Fons G, Hasibuan SM, Velden van der J, ten Kate FJ: Validation of tissue microarray technology in endometrioid cancer of the endometrium. J Clin Path. 2007, 60: 500-503. 10.1136/jcp.2006.040170.CrossRefPubMed

14.

Richani K, Romero R, Kim YM, Cushenberry E, Soto E, Han YM, Espinoza J, Kim CJ: Tissue microarray: an effective high-throughput method to study the placenta for clinical and research purposes. J Matern Fetal Neonatal Med. 2006, 19: 509-515. 10.1080/14767050600852718.CrossRefPubMed

15.

Friedrichs K, Gluba S, Eidtmann H, Jonat W: Overexpression of p53 and prognosis in breast cancer. Cancer. 1993, 72: 3641-3647. 10.1002/1097-0142(19931215)72:12<3641::AID-CNCR2820721215>3.0.CO;2-8.CrossRefPubMed

16.

Oremek GM, Sapoutzis N, Kramer W, Bickeboller R, Jonas D: Value of tumor M2 (Tu M2-PK) in patients with renal carcinoma. Anticancer Res. 2000, 20: 5095-5098.PubMed

17.

Oremek GM, Eigenbrodt E, Radle J, Zeuzem S, Seiffert UB: Value of the serum levels of the tumor marker TUM2-PK in pancreatic cancer. Anticancer Res. 1997, 17: 3031-3033.PubMed

18.

Kim C-W, Kim JI, Park S-H, Han J-Y, Kim JK, Chung KW, Sun HS: Usefulness of plasma tumor M2-pyruvate kinase in the diagnosis of gastrointestinal cancer. Korean J Gastroenterol. 2003, 42: 387-393.PubMed

19.

Roigas J, Deger S, Schroeder J, Wille A, Turk I, Brux B, Jung K, Schnorr D, Loening SA: Tumor type M2 pyruvate kinase expression in metastatic renal cell carcinoma. Urol Res. 2003, 31: 358-362. 10.1007/s00240-003-0331-4.CrossRefPubMed

20.

Zhang B, Chen J-Y, Chen D-D, Wang G-B, Shen P: Tumor type M2 pyruvate kinase expression in gastric cancer, colorectal cancer and controls. World J Gastroenterol. 2004, 10: 1643-1646.CrossRefPubMedPubMedCentral

21.

Luftner D, Mesterharm J, Akrivakis C, Geppert R, Petrides PE, Wernecke KD, Possinger K: Tumor type M2 pyruvate kinase expression in advanced breast cancer. Anticancer Res. 2000, 20: 5077-5082.PubMed

22.

Hardt PD, Ngoumou BK, Rupp J, Schnell-Kretschmer H, Kloer HU: Tumor M2-pyruvate kinase: a promising tumor marker in the diagnosis of gastro-intestinal cancer. Anticancer Res. 2000, 20: 4965-4968.PubMed

23.

Schneider J, Neu K, Velcovsky H-G, Morr H, Eigenbrodt E: Tumor M2-pyruvate kinase in the follow-up of inoperable lung cancer patients: a pilot study. Cancer Lett. 2003, 193: 91-98. 10.1016/S0304-3835(02)00720-6.CrossRefPubMed

24.

Cerwenka H, Aigner R, Bacher H, Werkgartner G, el-Shabrawi A, Quehenberger F, Mischinger HJ: TUM2-PK (pyruvate kinase type tumor M2), CA19-9 and CEA in patients with benign, malignant and metastasizing pancreatic lesions. Anticancer Res. 1999, 19: 849-851.PubMed

25.

Christofk HR, Heiden Vander MG, Harris MH, Ramanathan A, Gerszten RE, Wei R, Fleming MD, Schreiber SL, Cantley LC: The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature. 2008, 452: 230-233. 10.1038/nature06734.CrossRefPubMed

26.

Bergroth V, Reitamo S, Konttinen YT, E T: Fixation-dependent cytoplasmic false-positive staining with an immunoperoxidase method. Histochem Cell Biol. 1982, 73: 509-513. 10.1007/BF00493365.

27.

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: 28-31. 10.1515/CCLM.2006.006.CrossRefPubMed

28.

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: 1127-1130.PubMed

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/9/327/prepub

Title: Complete absence of M2-pyruvate kinase expression in benign pancreatic ductal epithelium and pancreaticobiliary and duodenal neoplasia
Authors: Mark M Aloysius
Abed M Zaitoun
Timothy E Bates
Abdulkader Albasri
Mohammad Ilyas
Brian J Rowlands
Dileep N Lobo
Publication date: 01-12-2009
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2009
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/1471-2407-9-327

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Abstract

Background

Methods

Results

Conclusion

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