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Langenbeck's Archives of Surgery

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01.11.2008 | Original Article

Molecular markers of pancreatic cancer: development and clinical relevance

verfasst von: Lucia C. Fry, Klaus Mönkemüller, Peter Malfertheiner

Erschienen in: Langenbeck's Archives of Surgery | Ausgabe 6/2008

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Abstract

Background

The prognosis of pancreatic cancer remains poor, mainly because of its aggressive biological behaviour and late clinical diagnosis, which precludes the application of appropriate curative therapies. Therefore, one of the major goals in clinical pancreatology is to find molecular markers, specific and sensitive enough to make an early and correct diagnosis of pancreatic cancer, before it has disseminated and become untreatable.

Objective

This overview article explores the potential utility of current molecular markers for the diagnosis of pancreatic cancer.

Results

There is a wide array of serum-based and tissue-based markers for pancreatic cancer. Serum-based molecular markers include CA 19-9, CA 125, M2-PK and secreted proteins. A tissue can be used to test genetic mutations such as K-ras, inactivation of tumour suppressor genes (e.g. p16, p53), mucins, telomerase activity, growth factors, DNA methylation, and global gene expression of cDNA microarrays, mitochondrial mutations and proteomics. None of these markers is currently useful for the detection of early pancreatic cancer. In clinical practice, the most commonly accepted use of CA 19-9 is to assess the prognosis and monitor the response to therapy.

Conclusions

Many molecular markers have been proposed for the early diagnosis of PC, but most are not ready to be included as part of the routine diagnostic algorithm because they still lack sensitivity, specificity or reproducibility. CA 19-9 remains the most useful molecular marker for the diagnosis and follow-up of clinically and radiological evident pancreatic cancer.

Warshaw AL, Fernandez-del Castillo C (1992) Pancreatic carcinoma. N Engl J Med 326:455–465PubMedCrossRef

American Gastroenterological Association, medical position statement (1999) Epidemiology, diagnosis, and treatment of pancreatic ductal adenocarcinoma. Gastroenterology 117:1463–1484CrossRef

Rosty C, Goggins M (2002) Early detection of pancreatic carcinoma. Hematol Oncol Clin North Am 16:37–52PubMedCrossRef

Oto A, Eltorky MA, Dave A, Ernst RD, Chen K, Rampy B, Chaljub G, Nealon W (2006) Mimicks of pancreatic malignancy in patients with chronic pancreatitis: correlation of computed tomography imaging features with histopathologic findings. Curr Probl Diagn Radiol 35:199–205PubMedCrossRef

Goggins M (2005) Molecular markers of early pancreatic cancer. J Clin Oncol 23:4524–4531PubMedCrossRef

Li D, Xie K, Wolff R, Abbruzzese JL (2004) Pancreatic cancer. Lancet 363:1049–1057PubMedCrossRef

Talar-Wojnarowska R, Malecka-Panas E (2006) Molecular pathogenesis of pancreatic adenocarcinoma: potential clinical implications. Med Sci Monit 12:RA186–RA193PubMed

Seufferlein T, Adler G (2005) What can be expected from tumor markers in pancreatic cancer. In: Dominguez-Muñoz JE (ed) Clinical pancreatology for practising gastroenterologist and surgeons. Blackwell, Malden, pp 377–382

Eloubeidi MA, Chen VK, Eltoum IA, Jhala D, Chhieng DC, Jhala N, Vickers SM, Wilcox CM (2003) Endoscopic ultrasound-guided fine needle aspiration biopsy of patients with suspected pancreatic cancer: diagnostic accuracy and acute and 30-day complications. Am J Gastroenterol 98:2663–2668PubMed

10.

Khalid A, Nodit L, Zahid M, Bauer K, Brody D, Finkelstein SD, McGrath KM (2006) Endoscopic ultrasound fine needle aspirate DNA analysis to differentiate malignant and benign pancreatic masses. Am J Gastroenterol 101:2493–2500PubMed

11.

Hruban RH, Goggins M, Parsons J, Kern SE (2000) Progression model for pancreatic cancer. Clin Cancer Res 6:2969–2972PubMed

12.

Cwik G, Wallner G, Skoczylas T, Ciechanski A, Zinkiewicz K (2006) Cancer antigens 19-9 and 125 in the differential diagnosis of pancreatic mass lesions. Arch Surg 141:968–973PubMedCrossRef

13.

Sawabu N, Watanabe H, Yamaguchi Y, Ohtsubo K, Motoo Y (2004) Serum tumor markers and molecular biological diagnosis in pancreatic cancer. Pancreas 28:263–267PubMedCrossRef

14.

Boeck S, Stieber P, Holdenrieder S, Wilkowski R, Heinemann V (2006) Prognostic and therapeutic significance of carbohydrate antigen 19-9 as tumor marker in patients with pancreatic cancer. Oncology 70:255–264PubMedCrossRef

15.

Tempero MA, Uchida E, Takasaki H, Burnett DA, Steplewski Z, Pour PM (1987) Relationship of carbohydrate antigen 19-9 and Lewis antigens in pancreatic cancer. Cancer Res 47:5501–5503PubMed

16.

Koprowski H, Brockhaus M, Blaszczyk M, Magnani J, Steplewski Z, Ginsburg V (1982) Lewis blood-type may affect the incidence of gastrointestinal cancer. Lancet 1:1332–1333PubMedCrossRef

17.

Steinberg W (1990) The clinical utility of the CA 19-9 tumor-associated antigen. Am J Gastroenterol 85:350–355PubMed

18.

Safi F, Schlosser W, Kolb G, Beger HG (1997) Diagnostic value of CA 19-9 in patients with pancreatic cancer and nonspecific gastrointestinal symptoms. J Gastrointest Surg 1:106–112PubMedCrossRef

19.

DiMagno EP, Reber HA, Tempero MA (1999) AGA technical review on the epidemiology, diagnosis, and treatment of pancreatic ductal adenocarcinoma: American Gastroenterological Association. Gastroenterology 117:1464–1484PubMedCrossRef

20.

Tomazic A, Pegan V (2000) Preoperative staging of periampullar cancer with US, CT, EUS and CA 19-9. Hepatogastroenterology 47:1135–1137PubMed

21.

DelMaschio A, Vanzulli A, Sironi S, Castrucci M, Mellone R, Staudacher C, Carlucci M, Zerbi A, Parolini D, Faravelli A (1991) Pancreatic cancer versus chronic pancreatitis: diagnosis with CA 19-9 assessment, US, CT, and CT-guided fine-needle biopsy. Radiology 178:95–99PubMed

22.

Yoshida EM, Scudamore CH, Erb SR, Owen DA, Silver HK (1995) Markedly elevated serum CA 19-9 levels in a case of chronic pancreatitis. Can J Surg 38:83–86PubMed

23.

Glenn J, Steinberg WM, Kurtzman SH, Steinberg SM, Sindelar WF (1988) Evaluation of the utility of a radioimmunoassay for serum CA 19-9 levels in patients before and after treatment of carcinoma of the pancreas. J Clin Oncol 6:462–468PubMed

24.

Jiang XT, Tao HQ, Zou SC (2004) Detection of serum tumor markers in the diagnosis and treatment of patients with pancreatic cancer. Hepatobiliary Pancreat Dis Int 3:464–468PubMed

25.

Montgomery RC, Hoffman JP, Riley LB, Rogatko A, Ridge JA, Eisenberg BL (1997) Prediction of recurrence and survival by post-resection CA 19-9 values in patients with adenocarcinoma of the pancreas. Ann Surg Oncol 4:551–556PubMedCrossRef

26.

Safi F, Schlosser W, Falkenreck S, Beger HG (1998) Prognostic value of CA 19-9 serum course in pancreatic cancer. Hepatogastroenterology 45:253–259PubMed

27.

Sperti C, Pasquali C, Catalini S, Cappellazzo F, Bonadimani B, Behboo R, Pedrazzoli S (1993) CA 19-9 as a prognostic index after resection for pancreatic cancer. J Surg Oncol 52:137–141PubMedCrossRef

28.

Lundin J, Roberts PJ, Kuusela P, Haglund C (1994) The prognostic value of preoperative serum levels of CA 19-9 and CEA in patients with pancreatic cancer. Br J Cancer 69:515–519PubMed

29.

Katz A, Hanlon A, Lanciano R, Hoffman J, Coia L (1998) Prognostic value of CA 19-9 levels in patients with carcinoma of the pancreas treated with radiotherapy. Int J Radiat Oncol Biol Phys 41:393–396PubMed

30.

Bassi C, Salvia R, Gumbs AA, Butturini G, Falconi M, Pederzoli P (2002) The value of standard serum tumor markers in differentiating mucinous from serous cystic tumors of the pancreas: CEA, CA 19-9, CA 125, CA 15-3. Langenbecks Arch Surg 387:281–285PubMedCrossRef

31.

Talbot RW, Nagorney DM, Pemberton JH, Wieand HS, Ritts RE Jr (1989) Comparison of portal and peripheral blood levels of carcinoembryonic antigen, CA 19-9, and CA 125 tumor-associated antigens in patients with colorectal and pancreatic cancer. Cancer Res 49:542–543PubMed

32.

Liu MP, Guo XZ, Xu JH, Wang D, Li HY, Cui ZM, Zhao JJ, Ren LN (2005) New tumor-associated antigen SC6 in pancreatic cancer. World J Gastroenterol 11:7671–7675PubMed

33.

Lluis F (2005) Genetic bases of pancreatic carcinogenesis: which concepts may be clinically relevant. In: Dominguez-Muñoz JE (ed) Clinical pancreatology for practising gastroenterologist and surgeons. Blackwell, Malden, pp 359–365

34.

Almoguera C, Shibata D, Forrester K, Martin J, Arnheim N, Perucho M (1988) Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell 53:549–554PubMedCrossRef

35.

Smit VT, Boot AJ, Smits AM, Fleuren GJ, Cornelisse CJ, Bos JL (1988) KRAS codon 12 mutations occur very frequently in pancreatic adenocarcinomas. Nucleic Acids Res 16:7773–7782PubMedCrossRef

36.

Berthelemy P, Bouisson M, Escourrou J, Vaysse N, Rumeau JL, Pradayrol L (1995) Identification of K-ras mutations in pancreatic juice in the early diagnosis of pancreatic cancer. Ann Intern Med 123:188–191PubMed

37.

Wenger FA, Zieren J, Peter FJ, Jacobi CA, Muller JM (1999) K-ras mutations in tissue and stool samples from patients with pancreatic cancer and chronic pancreatitis. Langenbecks Arch Surg 384:181–186PubMedCrossRef

38.

Trumper L, Menges M, Daus H, Kohler D, Reinhard JO, Sackmann M, Moser C, Sek A, Jacobs G, Zeitz M, Pfreundschuh M (2002) Low sensitivity of the ki-ras polymerase chain reaction for diagnosing pancreatic cancer from pancreatic juice and bile: a multicenter prospective trial. J Clin Oncol 20:4331–4337PubMedCrossRef

39.

Yamada T, Nakamori S, Ohzato H, Oshima S, Aoki T, Higaki N, Sugimoto K, Akagi K, Fujiwara Y, Nishisho I, Sakon M, Gotoh M, Monden M (1998) Detection of K-ras gene mutations in plasma DNA of patients with pancreatic adenocarcinoma: correlation with clinicopathological features. Clin Cancer Res 4:1527–1532PubMed

40.

Bramhall SR (1998) The use of molecular technology in the differentiation of pancreatic cancer and chronic pancreatitis. Int J Pancreatol 23:83–100PubMed

41.

Takahashi K, Yamao K, Okubo K, Sawaki A, Mizuno N, Ashida R, Koshikawa T, Ueyama Y, Kasugai K, Hase S, Kakumu S (2005) Differential diagnosis of pancreatic cancer and focal pancreatitis by using EUS-guided FNA. Gastrointest Endosc 61:76–79PubMedCrossRef

42.

Arvanitakis M, Van Laethem JL, Parma J, De Maertelaer V, Delhaye M, Deviere J (2004) Predictive factors for pancreatic cancer in patients with chronic pancreatitis in association with K-ras gene mutation. Endoscopy 36:535–542PubMedCrossRef

43.

Teich N, Mossner J (2004) Molecular analysis of pancreatic juice: a helpful tool to differentiate benign and malignant pancreatic tumors? Dig Dis 22:235–238PubMedCrossRef

44.

Boadas J, Mora J, Urgell E, Puig P, Roca M, Cusso X, Capella G, Lluis F, Farre A (2001) Clinical usefulness of K-ras gene mutation detection and cytology in pancreatic juice in the diagnosis and screening of pancreatic cancer. Eur J Gastroenterol Hepatol 13:1153–1159PubMedCrossRef

45.

Kim J, Reber HA, Dry SM, Elashoff D, Chen SL, Umetani N, Kitago M, Hines OJ, Kazanjian KK, Hiramatsu S, Bilchik AJ, Yong S, Shoup M, Hoon DS (2006) Unfavourable prognosis associated with K-ras gene mutation in pancreatic cancer surgical margins. Gut 55:1598–1605PubMedCrossRef

46.

Schutte M, Hruban RH, Geradts J, Maynard R, Hilgers W, Rabindran SK, Moskaluk CA, Hahn SA, Schwarte-Waldhoff I, Schmiegel W, Baylin SB, Kern SE, Herman JG (1997) Abrogation of the Rb/p16 tumor-suppressive pathway in virtually all pancreatic carcinomas. Cancer Res 57:3126–3130PubMed

47.

Wilentz RE, Geradts J, Maynard R, Offerhaus GJ, Kang M, Goggins M, Yeo CJ, Kern SE, Hruban RH (1998) Inactivation of the p16 (INK4A) tumor-suppressor gene in pancreatic duct lesions: loss of intranuclear expression. Cancer Res 58:4740–4744PubMed

48.

Ohtsubo K, Watanabe H, Yamaguchi Y, Hu YX, Motoo Y, Okai T, Sawabu N (2003) Abnormalities of tumor suppressor gene p16 in pancreatic carcinoma: immunohistochemical and genetic findings compared with clinicopathological parameters. J Gastroenterol 38:663–671PubMedCrossRef

49.

Redston MS, Caldas C, Seymour AB, Hruban RH, da Costa L, Yeo CJ, Kern SE (1994) p53 mutations in pancreatic carcinoma and evidence of common involvement of homocopolymer tracts in DNA microdeletions. Cancer Res 54:3025–3033PubMed

50.

Kirsch DG, Kastan MB (1998) Tumor-suppressor p53: implications for tumor development and prognosis. J Clin Oncol 16:3158–3168PubMed

51.

Casey G, Yamanaka Y, Friess H, Kobrin MS, Lopez ME, Buchler M, Beger HG, Korc M (1993) p53 mutations are common in pancreatic cancer and are absent in chronic pancreatitis. Cancer Lett 69:151–160PubMedCrossRef

52.

Sturm PD, Hruban RH, Ramsoekh TB, Noorduyn LA, Tytgat GN, Gouma DJ, Offerhaus GJ (1998) The potential diagnostic use of K-ras codon 12 and p53 alterations in brush cytology from the pancreatic head region. J Pathol 186:247–253PubMedCrossRef

53.

Yokoyama M, Yamanaka Y, Friess H, Buchler M, Korc M (1994) p53 expression in human pancreatic cancer correlates with enhanced biological aggressiveness. Anticancer Res 14:2477–2483PubMed

54.

Costentin L, Pages P, Bouisson M, Berthelemy P, Buscail L, Escourrou J, Pradayrol L, Vaysse N (2002) Frequent deletions of tumor suppressor genes in pure pancreatic juice from patients with tumoral or nontumoral pancreatic diseases. Pancreatology 2:17–25PubMedCrossRef

55.

Suehara N, Mizumoto K, Tanaka M, Niiyama H, Yokohata K, Tominaga Y, Shimura H, Muta T, Hamasaki N (1997) Telomerase activity in pancreatic juice differentiates ductal carcinoma from adenoma and pancreatitis. Clin Cancer Res 3:2479–2483PubMed

56.

Tsutsumi M, Tsujiuchi T, Ishikawa O, Majima T, Yoshimoto M, Sasaki Y, Fukuda T, Oohigashi H, Konishi Y (1997) Increased telomerase activities in human pancreatic duct adenocarcinomas. Jpn J Cancer Res 88:971–976PubMed

57.

Suehara N, Mizumoto K, Kusumoto M, Niiyama H, Ogawa T, Yamaguchi K, Yokohata K, Tanaka M (1998) Telomerase activity detected in pancreatic juice 19 months before a tumor is detected in a patient with pancreatic cancer. Am J Gastroenterol 93:1967–1971PubMedCrossRef

58.

Ohuchida K, Mizumoto K, Ishikawa N, Sato N, Nagai E, Yamaguchi K, Takaishi H, Ide T, Tanaka M (2004) A highly sensitive and quantitative telomerase activity assay with pancreatic juice is useful for diagnosis of pancreatic carcinoma without problems due to polymerase chain reaction inhibitors: analysis of 100 samples of pancreatic juice from consecutive patients. Cancer 101:2309–2317PubMedCrossRef

59.

Seki K, Suda T, Aoyagi Y, Sugawara S, Natsui M, Motoyama H, Shirai Y, Sekine T, Kawai H, Mita Y, Waguri N, Kuroiwa T, Igarashi M, Asakura H (2001) Diagnosis of pancreatic adenocarcinoma by detection of human telomerase reverse transcriptase messenger RNA in pancreatic juice with sample qualification. Clin Cancer Res 7:1976–1981PubMed

60.

Mizumoto K, Tanaka M (2005) Detection of telomerase activity in patients with pancreatic cancer. Methods Mol Med 103:199–205PubMed

61.

Ohuchida K, Mizumoto K, Yamada D, Yamaguchi H, Konomi H, Nagai E, Yamaguchi K, Tsuneyoshi M, Tanaka M (2006) Quantitative analysis of human telomerase reverse transcriptase in pancreatic cancer. Clin Cancer Res 12:2066–2069PubMedCrossRef

62.

Yamanaka Y, Friess H, Kobrin MS, Buchler M, Beger HG, Korc M (1993) Coexpression of epidermal growth factor receptor and ligands in human pancreatic cancer is associated with enhanced tumor aggressiveness. Anticancer Res 13:565–569PubMed

63.

Juhasz M, Nitsche B, Malfertheiner P, Ebert MP (2003) Implications of growth factor alterations in the treatment of pancreatic cancer. Mol Cancer 2:5PubMedCrossRef

64.

Wirtz M, Nyarangi J, Köninger J, Friess H (2005) Molecular basis of pancreatic carcinogenesis: which concepts may be clinically relevant. In: Dominguez-Muñoz JE (ed) Clinical pancreatology for practising gastroenterologist and surgeons. Blackwell, Malden, pp 351–358

65.

Friess H, Yamanaka Y, Buchler M, Ebert M, Beger HG, Gold LI, Korc M (1993) Enhanced expression of transforming growth factor beta isoforms in pancreatic cancer correlates with decreased survival. Gastroenterology 105:1846–1856PubMed

66.

Korc M, Chandrasekar B, Yamanaka Y, Friess H, Buchier M, Beger HG (1992) Overexpression of the epidermal growth factor receptor in human pancreatic cancer is associated with concomitant increases in the levels of epidermal growth factor and transforming growth factor alpha. J Clin Invest 90:1352–1360PubMedCrossRef

67.

Strous GJ, Dekker J (1992) Mucin-type glycoproteins. Crit Rev Biochem Mol Biol 27:57–92PubMedCrossRef

68.

Balague C, Gambus G, Carrato C, Porchet N, Aubert JP, Kim YS, Real FX (1994) Altered expression of MUC2, MUC4, and MUC5 mucin genes in pancreas tissues and cancer cell lines. Gastroenterology 106:1054–1061PubMed

69.

Andrianifahanana M, Moniaux N, Schmied BM, Ringel J, Friess H, Hollingsworth MA, Buchler MW, Aubert JP, Batra SK (2001) Mucin (MUC) gene expression in human pancreatic adenocarcinoma and chronic pancreatitis: a potential role of MUC4 as a tumor marker of diagnostic significance. Clin Cancer Res 7:4033–4040PubMed

70.

Han H, Bearss DJ, Browne LW, Calaluce R, Nagle RB, Von Hoff DD (2002) Identification of differentially expressed genes in pancreatic cancer cells using cDNA microarray. Cancer Res 62:2890–2896PubMed

71.

Hustinx SR, Cao D, Maitra A, Sato N, Martin ST, Sudhir D, Iacobuzio-Donahue C, Cameron JL, Yeo CJ, Kern SE, Goggins M, Mollenhauer J, Pandey A, Hruban RH (2004) Differentially expressed genes in pancreatic ductal adenocarcinomas identified through serial analysis of gene expression. Cancer Biol Ther 3:1254–1261PubMedCrossRef

72.

Iacobuzio-Donahue CA, Ashfaq R, Maitra A, Adsay NV, Shen-Ong GL, Berg K, Hollingsworth MA, Cameron JL, Yeo CJ, Kern SE, Goggins M, Hruban RH (2003) Highly expressed genes in pancreatic ductal adenocarcinomas: a comprehensive characterization and comparison of the transcription profiles obtained from three major technologies. Cancer Res 63:8614–8622PubMed

73.

Sato N, Maitra A, Fukushima N, van Heek NT, Matsubayashi H, Iacobuzio-Donahue CA, Rosty C, Goggins M (2003) Frequent hypomethylation of multiple genes overexpressed in pancreatic ductal adenocarcinoma. Cancer Res 63:4158–4166PubMed

74.

McCarthy DM, Maitra A, Argani P, Rader AE, Faigel DO, Van Heek NT, Hruban RH, Wilentz RE (2003) Novel markers of pancreatic adenocarcinoma in fine-needle aspiration: mesothelin and prostate stem cell antigen labeling increases accuracy in cytologically borderline cases. Appl Immunohistochem Mol Morphol 11:238–243PubMed

75.

Iacobuzio-Donahue CA, Maitra A, Shen-Ong GL, van Heek T, Ashfaq R, Meyer R, Walter K, Berg K, Hollingsworth MA, Cameron JL, Yeo CJ, Kern SE, Goggins M, Hruban RH (2002) Discovery of novel tumor markers of pancreatic cancer using global gene expression technology. Am J Pathol 160:1239–1249PubMed

76.

Honda K, Hayashida Y, Umaki T, Okusaka T, Kosuge T, Kikuchi S, Endo M, Tsuchida A, Aoki T, Itoi T, Moriyasu F, Hirohashi S, Yamada T (2005) Possible detection of pancreatic cancer by plasma protein profiling. Cancer Res 65:10613–10622PubMedCrossRef

77.

Bhattacharyya S, Siegel ER, Petersen GM, Chari ST, Suva LJ, Haun RS (2004) Diagnosis of pancreatic cancer using serum proteomic profiling. Neoplasia 6:674–686PubMedCrossRef

78.

Shen J, Person MD, Zhu J, Abbruzzese JL, Li D (2004) Protein expression profiles in pancreatic adenocarcinoma compared with normal pancreatic tissue and tissue affected by pancreatitis as detected by two-dimensional gel electrophoresis and mass spectrometry. Cancer Res 64:9018–9026PubMedCrossRef

79.

Koopmann J, Buckhaults P, Brown DA, Zahurak ML, Sato N, Fukushima N, Sokoll LJ, Chan DW, Yeo CJ, Hruban RH, Breit SN, Kinzler KW, Vogelstein B, Goggins M (2004) Serum macrophage inhibitory cytokine 1 as a marker of pancreatic and other periampullary cancers. Clin Cancer Res 10:2386–2392PubMedCrossRef

80.

Koopmann J, Rosenzweig CN, Zhang Z, Canto MI, Brown DA, Hunter M, Yeo C, Chan DW, Breit SN, Goggins M (2006) Serum markers in patients with resectable pancreatic adenocarcinoma: macrophage inhibitory cytokine 1 versus CA19-9. Clin Cancer Res 12:442–446PubMedCrossRef

81.

Maitra A, Cohen Y, Gillespie SE, Mambo E, Fukushima N, Hoque MO, Shah N, Goggins M, Califano J, Sidransky D, Chakravarti A (2004) The human MitoChip: a high-throughput sequencing microarray for mitochondrial mutation detection. Genome Res 14:812–819PubMedCrossRef

82.

Peng DF, Kanai Y, Sawada M, Ushijima S, Hiraoka N, Kitazawa S, Hirohashi S (2006) DNA methylation of multiple tumor-related genes in association with overexpression of DNA methyltransferase 1 (DNMT1) during multistage carcinogenesis of the pancreas. Carcinogenesis 27:1160–1168PubMedCrossRef

83.

Ueki T, Toyota M, Sohn T, Yeo CJ, Issa JP, Hruban RH, Goggins M (2000) Hypermethylation of multiple genes in pancreatic adenocarcinoma. Cancer Res 60:1835–1839PubMed

84.

Hustinx SR, Leoni LM, Yeo CJ, Brown PN, Goggins M, Kern SE, Hruban RH, Maitra A (2005) Concordant loss of MTAP and p16/CDKN2A expression in pancreatic intraepithelial neoplasia: evidence of homozygous deletion in a noninvasive precursor lesion. Mod Pathol 18:959–963PubMedCrossRef

85.

Fukushima N, Walter KM, Uek T, Sato N, Matsubayashi H, Cameron JL, Hruban RH, Canto M, Yeo CJ, Goggins M (2003) Diagnosing pancreatic cancer using methylation specific PCR analysis of pancreatic juice. Cancer Biol Ther 2:78–83PubMed

86.

Matsubayashi H, Canto M, Sato N, Klein A, Abe T, Yamashita K, Yeo CJ, Kalloo A, Hruban R, Goggins M (2006) DNA methylation alterations in the pancreatic juice of patients with suspected pancreatic disease. Cancer Res 66:1208–1217PubMedCrossRef

87.

Mazurek S, Boschek CB, Hugo F, Eigenbrodt E (2005) Pyruvate kinase type M2 and its role in tumor growth and spreading. Semin Cancer Biol 15:300–308PubMedCrossRef

88.

Ventrucci M, Cipolla A, Racchini C, Casadei R, Simoni P, Gullo L (2004) Tumor M2-pyruvate kinase, a new metabolic marker for pancreatic cancer. Dig Dis Sci 49:1149–1155PubMedCrossRef

Titel: Molecular markers of pancreatic cancer: development and clinical relevance
verfasst von: Lucia C. Fry
Klaus Mönkemüller
Peter Malfertheiner
Publikationsdatum: 01.11.2008
Verlag: Springer-Verlag
Erschienen in: Langenbeck's Archives of Surgery / Ausgabe 6/2008
Print ISSN: 1435-2443
Elektronische ISSN: 1435-2451
DOI: https://doi.org/10.1007/s00423-007-0276-0

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