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Mucin expression profile in pancreatic cancer and the precursor lesions

  • Kohji Nagata
  • Michiko Horinouchi
  • Miyuki Saitou
  • Michiyo Higashi
  • Mitsuharu Nomoto
  • Masamichi Goto
  • Suguru Yonezawa
Topics: Current understanding of precursors to pancreatic cancer

Abstract

In this review article, we demonstrate the mucin expression profile in normal tissue, invasive ductal carcinoma (IDC), two subtypes of intraductal papillary–mucinous neoplasm (IPMN dark cell type and IPMN clear cell type), pancreatic intraepithelial neoplasia (PanIN), and mucinous cystic neoplasm (MCN) of the pancreas. In MUC1, there are various glycoforms, such as poorly glycosylated MUC1, sialylated MUC1, and fully glycosylated MUC1. IDCs showed high expression of all the glycoforms of MUC1. IPMNs dark cell type showed no expression or low expression of all the glycoforms of MUC1. IPMNs clear cell type showed low expression of poorly glycosylated MUC1, but expression of sialylated MUC1 and fully glycosylated MUC1. Expression of MUC2 was negative in IDCs, high in IPMNs dark cell type and low in IPMNs clear cell type. MUC5AC was highly expressed in IDCs, IPMNs dark cell type, and IPMNs clear cell type. MUC6 expression was higher in IPMNs clear cell type than in IDCs and IPMNs dark cell type. Our recent study demonstrated that high expression of MUC4 in IDCs is correlated with a poor outcome for patients. In PanINs, expression of both MUC5AC and MUC6 are an early event, whereas up-regulation of MUC1 is a late event. MCNs do not look as if they will show a specific mucin expression profile according to the literature review.

Key words

Pancreas Invasive ductal carcinoma Intraductal–papillary mucinous neoplasm Pancreatic intraepithelial neoplasia Mucinous cystic neoplasm Mucin 

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References

  1. 1.
    Isaji, S, Kawarada, Y, Uemoto, S 2004Classification of pancreatic cancer: comparison of Japanese and UICC classificationsPancreas282314PubMedCrossRefGoogle Scholar
  2. 2.
    Yonezawa, S, Sato, E 1997Expression of mucin antigens in human cancers and its relationship with malignancy potentialPathol Int4781330PubMedGoogle Scholar
  3. 3.
    Lehmann, JM, Riethmuller, G, Johnson, JP 1989MUC18, a marker of tumor progression in human melanoma, shows sequence similarity to the neural cell adhesion molecules of the immunoglobulin superfamilyProc Natl Acad Sci USA8698915PubMedCrossRefGoogle Scholar
  4. 4.
    D'Cruz, OJ, Dunn, TS, Pichan, P, Hass, GG,Jr, Sachdev, GP 1996Antigenic cross-reactivity of human tracheal mucin with human sperm and trophoblasts correlates with the expression of mucin 8 gene messenger ribonucleic acid in reproductive tract tissuesFertil Steril6631626PubMedGoogle Scholar
  5. 5.
    Lapensee, L, Paquette, Y, Bleau, G 1997Allelic polymorphism and chromosomal localization of the human oviductin gene (MUC9)Fertil Steril687028PubMedCrossRefGoogle Scholar
  6. 6.
    Williams, SJ, McGuckin, MA, Gotley, DC, Eyre, HJ, Sutherland, GR, Antalis, TM 1999Two novel mucin genes down-regulated in colorectal cancer identified by differential displayCancer Res5940839PubMedGoogle Scholar
  7. 7.
    Williams, SJ, Wreschner, DH, Tran, M, Eyre, HJ, Sutherland, GR, McGuckin, MA 2001Muc13, a novel human cell surface mucin expressed by epithelial and hemopoietic cellsJ Biol Chem2761832736PubMedCrossRefGoogle Scholar
  8. 8.
    Pallesen, LT, Berglund, L, Rasmussen, LK, Petersen, TE, Rasmussen, JT 2002Isolation and characterization of MUC15, a novel cell membrane-associated mucinEur J Biochem269275563PubMedCrossRefGoogle Scholar
  9. 9.
    Yin, BW, Dnistrian, A, Lloyd, KO 2002Ovarian cancer antigen CA125 is encoded by the MUC16 mucin geneInt J Cancer9873740PubMedCrossRefGoogle Scholar
  10. 10.
    Gum, JR,Jr, Crawley, SC, Hicks, JW, Szymkowski, DE, Kim, YS 2002MUC17, a novel membrane-tethered mucinBiochem Biophys Res Commun29146675PubMedCrossRefGoogle Scholar
  11. 11.
    Chen, Y, Zhao, YH, Kalaslavadi, TB, Hamati, E, Nehrke, K, Le, AD,  et al. 2004Genome-wide search and identification of a novel gel-forming mucin MUC19/Muc19 in glandular tissuesAm J Respir Cell Mol Biol3015565PubMedCrossRefGoogle Scholar
  12. 12.
    Higuchi, T, Orita, T, Nakanishi, S, Katsuya, K, Watanabe, H, Yamasaki, Y,  et al. 2004Molecular cloning, genomic structure, and expression analysis of MUC20, a novel mucin protein, up-regulated in injured kidneyJ Biol Chem279196879PubMedCrossRefGoogle Scholar
  13. 13.
    Sasaki, M, Ikeda, H, Nakanuma, Y 2005Expression profiles of MUC mucin core protein in the intrahepatic biliary system: physiological distribution and pathological significanceActa Histochem Cytochem38295303CrossRefGoogle Scholar
  14. 14.
    Moniaux, N, Escande, F, Porchet, N, Aubert, JP, Batra, SK 2001Structural organization and classification of the human mucin genesFront Biosci6D1192206PubMedCrossRefGoogle Scholar
  15. 15.
    Osako, M, Yonezawa, S, Siddiki, B, Huang, J, Ho, JJ, Kim, YS,  et al. 1993Immunohistochemical study of mucin carbohydrates and core proteins in human pancreatic tumorsCancer7121919PubMedCrossRefGoogle Scholar
  16. 16.
    Utsunomiya, T, Yonezawa, S, Sakamoto, H, Kitamura, H, Hokita, S, Aiko, T,  et al. 1998Expression of MUC1 and MUC2 mucins in gastric carcinomas: its relationship with the prognosis of the patientsClin Cancer Res4260514PubMedGoogle Scholar
  17. 17.
    Higashi, M, Yonezawa, S, Ho, JJ, Tanaka, S, Irimura, T, Kim, YS,  et al. 1999Expression of MUC1 and MUC2 mucin antigens in intrahepatic bile duct tumors: its relationship with a new morphological classification of cholangiocarcinomaHepatology30134755PubMedCrossRefGoogle Scholar
  18. 18.
    Sagara, M, Yonezawa, S, Nagata, K, Tezuka, Y, Natsugoe, S, Xing, PX,  et al. 1999Expression of mucin 1 (MUC1) in esophageal squamous-cell carcinoma: its relationship with prognosisInt J Cancer842517PubMedCrossRefGoogle Scholar
  19. 19.
    Yonezawa, S, Nakamura, A, Horinouchi, M, Sato, E 2002The expression of several types of mucin is related to the biological behavior of pancreatic neoplasmsJ Hepatobiliary Pancreat Surg932841PubMedCrossRefGoogle Scholar
  20. 20.
    Tamada, S, Goto, M, Nomoto, M, Nagata, K, Shimizu, T, Tanaka, S,  et al. 2002Expression of MUC1 and MUC2 mucins in extrahepatic bile duct carcinomas: its relationship with tumor progression and prognosisPathol Int5271323PubMedCrossRefGoogle Scholar
  21. 21.
    Nakamura, A, Horinouchi, M, Goto, M, Nagata, K, Sakoda, K, Takao, S,  et al. 2002New classification of pancreatic intraductal papillary–mucinous tumour by mucin expression: its relationship with potential for malignancyJ Pathol19720110PubMedCrossRefGoogle Scholar
  22. 22.
    Matsukita, S, Nomoto, M, Kitajima, S, Tanaka, S, Goto, M, Irimura, T,  et al. 2003Expression of mucins (MUC1, MUC2, MUC5AC, and MUC6) in mucinous carcinoma of the breast: comparison with invasive ductal carcinomaHistopathology422636PubMedCrossRefGoogle Scholar
  23. 23.
    Nagata, K 2005Analysis of mucins and CD10 expression in pancreatic intraductal neoplasia (in Japanese, with English abstract)Kagoshimadaigaku Igakuzashi (Med J Kagoshima Univ)57717Google Scholar
  24. 24.
    Yonezawa, S, Horinouchi, M, Osako, M, Kubo, M, Takao, S, Arimura, Y,  et al. 1999Gene expression of gastric type mucin (MUC5AC) in pancreatic tumors: its relationship with the biological behavior of the tumorPathol Int494554PubMedCrossRefGoogle Scholar
  25. 25.
    Horinouchi, M, Nagata, K, Nakamura, A, Goto, M, Takao, S, Sakamoto, M,  et al. 2003Expression of different glycoforms of membrane mucin (MUC1) and secretory mucin (MUC2, MUC5AC and MUC6) in pancreatic neoplasmsActa Histochem Cytochem36443453CrossRefGoogle Scholar
  26. 26.
    Fukushima, N, Mukai, K, Kanai, Y, Hasebe, T, Shimada, K, Ozaki, H,  et al. 1997Intraductal papillary tumors and mucinous cystic tumors of the pancreas: clinicopathologic study of 38 casesHum Pathol2810107PubMedCrossRefGoogle Scholar
  27. 27.
    Adsay, NV, Conlon, KC, Zee, SY, Brennan, MF, Klimstra, DS 2002Intraductal papillary–mucinous neoplasms of the pancreas: an analysis of in situ and invasive carcinomas in 28 patientsCancer946277PubMedCrossRefGoogle Scholar
  28. 28.
    Kim, GE, Bae, HI, Park, HU, Kuan, SF, Crawley, SC, Ho, JJ,  et al. 2002Aberrant expression of MUC5AC and MUC6 gastric mucins and sialyl Tn antigen in intraepithelial neoplasms of the pancreasGastroenterology123105260PubMedCrossRefGoogle Scholar
  29. 29.
    Biankin, AV, Kench, JG, Morey, AL, Lee, CS, Biankin, SA, Head, DR,  et al. 2001Overexpression of p21(WAF1/CIP1) is an early event in the development of pancreatic intraepithelial neoplasiaCancer Res6188307PubMedGoogle Scholar
  30. 30.
    Sessa, F, Solcia, E, Capella, C, Bonato, M, Scarpa, A, Zamboni, G,  et al. 1994Intraductal papillary–mucinous tumours represent a distinct group of pancreatic neoplasms: an investigation of tumour cell differentiation and K-ras, p53 and c-erbB-2 abnormalities in 26 patientsVirchows Arch42535767PubMedCrossRefGoogle Scholar
  31. 31.
    Biankin, AV, Kench, JG, Biankin, SA, Lee, CS, Morey, AL, Dijkman, FP,  et al. 2004Pancreatic intraepithelial neoplasia in association with intraductal papillary mucinous neoplasms of the pancreas: implications for disease progression and recurrenceAm J Surg Pathol28118492PubMedCrossRefGoogle Scholar
  32. 32.
    Moriya, T, Kimura, W, Semba, S, Sakurai, F, Hirai, I, Ma, J,  et al. 2005Biological similarities and differences between pancreatic intraepithelial neoplasias and intraductal papillary mucinous neoplasmsInt J Gastrointest Cancer351119PubMedCrossRefGoogle Scholar
  33. 33.
    Rosty, C, Geradts, J, Sato, N, Wilentz, RE, Roberts, H, Sohn, T,  et al. 2003p16 inactivation in pancreatic intraepithelial neoplasias (PanINs) arising in patients with chronic pancreatitisAm J Surg Pathol271495501PubMedCrossRefGoogle Scholar
  34. 34.
    McCarthy, DM, Brat, DJ, Wilentz, RE, Yeo, CJ, Cameron, JL, Kern, SE,  et al. 2001Pancreatic intraepithelial neoplasia and infiltrating adenocarcinoma: analysis of progression and recurrence by DPC4 immunohistochemical labelingHum Pathol3263842PubMedCrossRefGoogle Scholar
  35. 35.
    Goggins, M, Hruban, RH, Kern, SE 2000BRCA2 is inactivated late in the development of pancreatic intraepithelial neoplasia: evidence and implicationsAm J Pathol156176771PubMedGoogle Scholar
  36. 36.
    Yoshizawa, K, Nagai, H, Sakurai, S, Hironaka, M, Morinaga, S, Saitoh, K,  et al. 2002Clonality and K-ras mutation analyses of epithelia in intraductal papillary mucinous tumor and mucinous cystic tumor of the pancreasVirchows Arch44143743PubMedCrossRefGoogle Scholar
  37. 37.
    Luttges, J, Feyerabend, B, Buchelt, T, Pacena, M, Kloppel, G 2002The mucin profile of noninvasive and invasive mucinous cystic neoplasms of the pancreasAm J Surg Pathol2646671PubMedCrossRefGoogle Scholar
  38. 38.
    Iacobuzio-Donahue, CA, Klimstra, DS, Adsay, NV, Wilentz, RE, Argani, P, Sohn, TA,  et al. 2000Dpc-4 protein is expressed in virtually all human intraductal papillary mucinous neoplasms of the pancreas: comparison with conventional ductal adenocarcinomasAm J Pathol15775561PubMedGoogle Scholar
  39. 39.
    Schwarte-Waldhoff, I, Volpert, OV, Bouck, NP, Sipos, B, Hahn, SA, Klein-Scory, S,  et al. 2000Smad4/DPC4-mediated tumor suppression through suppression of angiogenesisProc Natl Acad Sci USA9796249PubMedCrossRefGoogle Scholar
  40. 40.
    Jimenez, RE, Warshaw, AL, Z'Graggen, K, Hartwig, W, Taylor, DZ, Compton, CC,  et al. 1999Sequential accumulation of K-ras mutations and p53 overexpression in the progression of pancreatic mucinous cystic neoplasms to malignancyAnn Surg2305019discussion 509–11PubMedCrossRefGoogle Scholar
  41. 41.
    Bartsch, D, Bastian, D, Barth, P, Schudy, A, Nies, C, Kisker, O,  et al. 1998K-ras oncogene mutations indicate malignancy in cystic tumors of the pancreasAnn Surg2287986PubMedCrossRefGoogle Scholar
  42. 42.
    Zhao, J, Liang, SX, Savas, L, Banner, BF 2001An immunostaining panel for diagnosis of malignancy in mucinous tumors of the pancreasArch Pathol Lab Med1257659PubMedGoogle Scholar
  43. 43.
    Kim, SG, Wu, TT, Lee, JH, Yun, YK, Issa, JP, Hamilton, SR,  et al. 2003Comparison of epigenetic and genetic alterations in mucinous cystic neoplasm and serous microcystic adenoma of pancreasMod Pathol16108694PubMedCrossRefGoogle Scholar
  44. 44.
    Maitra, A, Adsay, NV, Argani, P, Iacobuzio-Donahue, C, De Marzo, A, Cameron, JL,  et al. 2003Multicomponent analysis of the pancreatic adenocarcinoma progression model using a pancreatic intraepithelial neoplasia tissue microarrayMod Pathol1690212PubMedCrossRefGoogle Scholar
  45. 45.
    Chetty, R, Serra, S, Salahshor, S, Alsaad, K, Shih, W, Blaszyk, H,  et al. 2006Expression of Wnt-signaling pathway proteins in intraductal papillary mucinous neoplasms of the pancreas: a tissue microarray analysisHum Pathol372127PubMedCrossRefGoogle Scholar
  46. 46.
    Biankin, AV, Biankin, SA, Kench, JG, Morey, AL, Lee, CS, Head, DR,  et al. 2002Aberrant p16(INK4A) and DPC4/Smad4 expression in intraductal papillary mucinous tumours of the pancreas is associated with invasive ductal adenocarcinomaGut508618PubMedCrossRefGoogle Scholar
  47. 47.
    Bardeesy, N, DePinho, RA 2002Pancreatic cancer biology and geneticsNat Rev Cancer2897909PubMedCrossRefGoogle Scholar
  48. 48.
    Clayton, F 1986Pure mucinous carcinomas of breast: morphologic features and prognostic correlatesHum Pathol17348PubMedCrossRefGoogle Scholar
  49. 49.
    Nakamori, S, Ota, DM, Cleary, KR, Shirotani, K, Irimura, T 1994MUC1 mucin expression as a marker of progression and metastasis of human colorectal carcinomaGastroenterology10635361PubMedGoogle Scholar
  50. 50.
    Yonezawa, S 1994Application of immunohistochemistry for diagnosis of neoplasms: mucin antigens expression and biological behavior of neoplasmsActa Histochem Cytochem2756166Google Scholar
  51. 51.
    Balague, C, Audie, JP, Porchet, N, Real, FX 1995In situ hybridization shows distinct patterns of mucin gene expression in normal, benign, and malignant pancreas tissuesGastroenterology10995364PubMedCrossRefGoogle Scholar
  52. 52.
    Terris, B, Dubois, S, Buisine, MP, Sauvanet, A, Ruszniewski, P, Aubert, JP,  et al. 2002Mucin gene expression in intraductal papillary–mucinous pancreatic tumours and related lesionsJ Pathol1976327PubMedCrossRefGoogle Scholar
  53. 53.
    Adsay, NV 2002Intraductal papillary–mucinous neoplasms of the pancreas: pathology and molecular geneticsJ Gastrointest Surg66569PubMedCrossRefGoogle Scholar
  54. 54.
    Adsay, NV, Merati, K, Andea, A, Sarkar, F, Hruban, RH, Wilentz, RE,  et al. 2002The dichotomy in the preinvasive neoplasia to invasive carcinoma sequence in the pancreas: differential expression of MUC1 and MUC2 supports the existence of two separate pathways of carcinogenesisMod Pathol15108795PubMedCrossRefGoogle Scholar
  55. 55.
    Gum, JR,Jr 1992Mucin genes and the proteins they encode: structure, diversity, and regulationAm J Respir Cell Mol Biol755764PubMedGoogle Scholar
  56. 56.
    Gum, JR,Jr, Hicks, JW, Toribara, NW, Siddiki, B, Kim, YS 1994Molecular cloning of human intestinal mucin (MUC2) cDNA. Identification of the amino terminus and overall sequence similarity to prepro-von Willebrand factorJ Biol Chem26924406PubMedGoogle Scholar
  57. 57.
    Kim, YS, Gum, JR,Jr 1995Diversity of mucin genes, structure, function, and expressionGastroenterology1099991001PubMedCrossRefGoogle Scholar
  58. 58.
    Buisine, MP, Janin, A, Maunoury, V, Audie, JP, Delescaut, MP, Copin, MC,  et al. 1996Aberrant expression of a human mucin gene (MUC5AC) in rectosigmoid villous adenomaGastroenterology1108491PubMedCrossRefGoogle Scholar
  59. 59.
    Pigny, P, Guyonnet-Duperat, V, Hill, AS, Pratt, WS, Galiegue-Zouitina, S, d'Hooge, MC,  et al. 1996Human mucin genes assigned to 11p15.5: identification and organization of a cluster of genesGenomics3834052PubMedCrossRefGoogle Scholar
  60. 60.
    Ho, SB, Roberton, AM, Shekels, LL, Lyftogt, CT, Niehans, GA, Toribara, NW 1995Expression cloning of gastric mucin complementary DNA and localization of mucin gene expressionGastroenterology10973547PubMedCrossRefGoogle Scholar
  61. 61.
    De Bolos, C, Garrido, M, Real, FX 1995MUC6 apomucin shows a distinct normal tissue distribution that correlates with Lewis antigen expression in the human stomachGastroenterology10972334PubMedCrossRefGoogle Scholar
  62. 62.
    Ho, JJ, Han, SW, Pan, PL, Deng, G, Kuan, SF, Kim, YS 2003Methylation status of promoters and expression of MUC2 and MUC5AC mucins in pancreatic cancer cellsInt J Oncol222739PubMedGoogle Scholar
  63. 63.
    Yonezawa, S, Taira, M, Osako, M, Kubo, M, Tanaka, S, Sakoda, K,  et al. 1998MUC-1 mucin expression in invasive areas of intraductal papillary mucinous tumors of the pancreasPathol Int4831922PubMedCrossRefGoogle Scholar
  64. 64.
    Shibahara, H, Tamada, S, Higashi, M, Goto, M, Batra, SK, Hollingsworth, M,  et al. 2004MUC4 is a novel prognostic factor of intrahepatic cholangiocarcinoma mass-forming typeHepatology392209PubMedCrossRefGoogle Scholar
  65. 65.
    Saitou, M, Goto, M, Horinouchi, M, Tamada, S, Nagata, K, Hamada, T,  et al. 2005MUC4 expression is a novel prognostic factor in patients with invasive ductal carcinoma of the pancreasJ Clin Pathol5884552PubMedCrossRefGoogle Scholar
  66. 66.
    Ramsauer, VP, Carraway, CA, Salas, PJ, Carraway, KL 2003Muc4/sialomucin complex, the intramembrane ErbB2 ligand, translocates ErbB2 to the apical surface in polarized epithelial cellsJ Biol Chem278301427PubMedCrossRefGoogle Scholar
  67. 67.
    Jepson, S, Komatsu, M, Haq, B, Arango, ME, Huang, D, Carraway, CA,  et al. 2002Muc4/sialomucin complex, the intramembrane ErbB2 ligand, induces specific phosphorylation of ErbB2 and enhances expression of p27(kip), but does not activate mitogen-activated kinase or protein kinaseB/Akt pathwaysOncogene21752432PubMedCrossRefGoogle Scholar
  68. 68.
    DiGiovanna, MP, Stern, DF 1995Activation state-specific monoclonal antibody detects tyrosine phosphorylated p185neu/erbB-2 in a subset of human breast tumors overexpressing this receptorCancer Res55194655PubMedGoogle Scholar
  69. 69.
    Carraway, KL, Ramsauer, VP, Haq, B, Carothers Carraway, CA 2003Cell signaling through membrane mucinsBioessays256671PubMedCrossRefGoogle Scholar
  70. 70.
    Singh, AP, Moniaux, N, Chauhan, SC, Meza, JL, Batra, SK 2004Inhibition of MUC4 expression suppresses pancreatic tumor cell growth and metastasisCancer Res6462230PubMedCrossRefGoogle Scholar
  71. 71.
    Half, E, Broaddus, R, Danenberg, KD, Danenberg, PV, Ayers, GD, Sinicrope, FA 2004HER-2 receptor expression, localization, and activation in colorectal cancer cell lines and human tumorsInt J Cancer1085408PubMedCrossRefGoogle Scholar
  72. 72.
    Sgambato, A, Migaldi, M, Leocata, P, Ventura, L, Criscuolo, M, Di Giacomo, C,  et al. 2000Loss of p27Kip1 expression is a strong independent prognostic factor of reduced survival in N0 gastric carcinomasCancer89224757PubMedCrossRefGoogle Scholar
  73. 73.
    Chen, AJ, Meng, QH, Long, B, Yang, GL 2002Relationship between p27 expression and prognosis of colorectal carcinomaAi Zheng2110757PubMedGoogle Scholar
  74. 74.
    Taguchi, K, Aishima, S, Asayama, Y, Kajiyama, K, Kinukawa, N, Shimada, M,  et al. 2001The role of p27kip1 protein expression on the biological behavior of intrahepatic cholangiocarcinomaHepatology33111823PubMedCrossRefGoogle Scholar
  75. 75.
    Moniaux, N, Nollet, S, Porchet, N, Degand, P, Laine, A, Aubert, JP 1999Complete sequence of the human mucin MUC4: a putative cell membrane-associated mucinBiochem J33832533PubMedCrossRefGoogle Scholar
  76. 76.
    Komatsu, M, Yee, L, Carraway, KL 1999Overexpression of sialomucin complex, a rat homologue of MUC4, inhibits tumor killing by lymphokine-activated killer cellsCancer Res59222936PubMedGoogle Scholar
  77. 77.
    Komatsu, M, Carraway, CA, Fregien, NL, Carraway, KL 1997Reversible disruption of cell–matrix and cell–cell interactions by overexpression of sialomucin complexJ Biol Chem2723324554PubMedCrossRefGoogle Scholar
  78. 78.
    Hruban, RH, Adsay, NV, Albores-Saavedra, J, Compton, C, Garrett, ES, Goodman, SN,  et al. 2001Pancreatic intraepithelial neoplasia: a new nomenclature and classification system for pancreatic duct lesionsAm J Surg Pathol2557986PubMedCrossRefGoogle Scholar
  79. 79.
    Swartz, MJ, Batra, SK, Varshney, GC, Hollingsworth, MA, Yeo, CJ, Cameron, JL,  et al. 2002MUC4 expression increases progressively in pancreatic intraepithelial neoplasiaAm J Clin Pathol1177916PubMedCrossRefGoogle Scholar
  80. 80.
    Park, HU, Kim, JW, Kim, GE, Bae, HI, Crawley, SC, Yang, SC,  et al. 2003Aberrant expression of MUC3 and MUC4 membrane-associated mucins and sialyl Le(x) antigen in pancreatic intraepithelial neoplasiaPancreas26e4854PubMedCrossRefGoogle Scholar
  81. 81.
    Terada, T, Ohta, T, Sasaki, M, Nakanuma, Y, Kim, YS 1996Expression of MUC apomucins in normal pancreas and pancreatic tumoursJ Pathol1801605PubMedCrossRefGoogle Scholar
  82. 82.
    Zamboni, G, Scarpa, A, Bogina, G, Iacono, C, Bassi, C, Talamini, G,  et al. 1999Mucinous cystic tumors of the pancreas: clinicopathological features, prognosis, and relationship to other mucinous cystic tumorsAm J Surg Pathol2341022PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Tokyo 2007

Authors and Affiliations

  • Kohji Nagata
    • 1
  • Michiko Horinouchi
    • 1
  • Miyuki Saitou
    • 1
  • Michiyo Higashi
    • 1
  • Mitsuharu Nomoto
    • 1
  • Masamichi Goto
    • 1
  • Suguru Yonezawa
    • 1
  1. 1.Department of Human Pathology, Field of OncologyKagoshima University Graduate School of Medical and Dental SciencesKagoshimaJapan

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