Current understanding of precursors to pancreatic cancer

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• 作者：Kyoichi Takaori (A1)
  
• 关键词：PanIN (pancreatic intraepithelial neoplasia) ; IPMN (intraductal papillary mucinous neoplasm) ; MCN (mucinous cystic neoplasm) ; Carcinoma in situ ; Carcinogenesis
• 刊名：Journal of Hepato-Biliary-Pancreatic Sciences
• 出版年：2007
• 出版时间：May 2007
• 年：2007
• 卷：14
• 期：3
• 页码：217-223
• 全文大小：392KB
• 参考文献：1. Parkin, DM, Bray, F, Ferlay, J, Pisani, P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55: pp. 74-108 CrossRef
  2. Takada, T (1999) Surgery for carcinoma of the pancreas in Japan. Past, present, and future aspects. Digestion 60: pp. 114-9 CrossRef
  3. Nguyen, TC, Sohn, TA, Cameron, JL, Lillemoe, KD, Campbell, KA, Coleman, J (2003) Standard vs. radical pancreaticoduodenectomy for periampullary adenocarcinoma: a prospective, randomized trial evaluating quality of life in pancreaticoduodenectomy survivors. J Gastrointest Surg 7: pp. 1-9 CrossRef
  4. Yeo, CJ, Cameron, JL, Lillemoe, KD, Sohn, TA, Campbell, KA, Sauter, PK (2002) Pancreaticoduodenectomy with or without distal gastrectomy and extended retroperitoneal lymphadenectomy for periampullary adenocarcinoma. Part 2. Randomized controlled trial evaluating survival, morbidity, and mortality. Ann Surg 236: pp. 355-66 CrossRef
  5. Matsuno, S, Egawa, S, Arai, K (2001) Trends in treatment for pancreatic cancer. J Hepatobiliary Pancreat Surg 8: pp. 544-8 CrossRef
  6. Isozaki, H, Okajima, K, Morita, S, Takeda, Y, Ishibashi, T, Tanimura, M (1990) Review of pancreatic cancer. Bull Osaka Med Coll 36: pp. 1-11
  7. Fujikawa, T, Matsusue, S, Hasegawa, S, Asao, Y, Kato, Y, Takaori, K (1999) Intraoperative radiation therapy (IORT) for pancreatic cancer. Tenri Med Bull 2: pp. 20-31
  8. Takaori, K, Hruban, RH, Maitra, A, Tanigawa, N (2004) Pancreatic intraepithelial neoplasia. Pancreas 28: pp. 257-62 CrossRef
  9. Ishikawa, O, Ohigashi, H, Imaoka, S, Nakaizumi, A, Uehara, H, Kitamura, T (1999) Minute carcinoma of the pancreas measuring 1?cm or less in diameter: collective review of Japanese case reports. Hepatogastroenterology 46: pp. 8-15
  10. Maitra, A, Fukushima, N, Takaori, K, Hruban, RH (2005) Precursors to invasive pancreatic cancer. Adv Anat Pathol 12: pp. 81-91 CrossRef
  11. Feldmann, G, Beaty, R, Hruban, RH, Maitra, A (2007) Molecular genetics of pancreatic intraepithelial neoplasia. J Hepatobiliary Pancreat Surg 14: pp. 224-32
  12. Furukawa, T (2007) Molecular genetics of intraductal papillary-mucinous neoplasms of the pancreas. J Hepatobiliary Pancreat Surg 14: pp. 233-7
  13. Fukushima, N, Fukayama, M (2007) Mucinous cystic neoplasms of the pancreas: pathology and molecular genetics. J Hepatobiliary Pancreat Surg 14: pp. 238-42
  14. Nagata, K, Horinouchi, M, Higashi, M, Nomoto, M, Goto, M, Yonezawa, S (2007) Mucins expression profile in pancreatic cancer and the precursor lesions. J Hepatobiliary Pancreat Surg 14: pp. 243-54
  15. Hruban, RH, Takaori, K, Canto, M, Fishman, EK, Campbell, K, Brune, K (2007) The clinical importance of precursor lesions in the pancreas. J Hepatobiliary Pancreat Surg 14: pp. 255-63
  16. Kl?ppel, G, Solcia, E, Longnecker, DS, Capella, C, Sobin, LH (1996) Histological typing of tumours of the exocrine pancreas. Springer, Berlin
  17. Hulst, SPL (1905) Zur kenntnis der Genese des Adenokarzinoms und Karzinoms des Pankreas. Virchows Arch (B) 180: pp. 288-316
  18. Kozuka, S, Sassa, R, Taki, T, Masamoto, K, Nagasawa, S, Saga, S (1979) Relation of pancreatic duct hyperplasia to carcinoma. Cancer 43: pp. 1418-28 CrossRef
  19. Compagno, J, Oertel, JE (1978) Mucinous cystic neoplasms of the pancreas with overt and latent malignancy (cystadenocarcinoma and cystadenoma). A clinicopathologic study of 41 cases. Am J Clin Pathol 69: pp. 573-80
  20. Ohhashi, K, Murakami, Y, Takekoshi, T (1982) Four cases of “mucin-producing-cancer of the pancreas on specific findings of the papilla of Vater (in Japanese with English abstract). Prog Diagn Endosc 20: pp. 348-51
  21. Zamboni, G, Kl?ppel, G, Hruban, RH, Longnecker, DS, Adler, G Mucinous cystic neoplasms of the pancreas. In: Hamilton, SR, Aaltonen, LA eds. (2000) World Health Organization classification of tumours. pathology and genetics of tumours of the digestive system. IAPC, Lyon, pp. 234-6
  22. Kuroda, A (1988) Recent progress in clinicopathology of pancreatic tumors (in Japanese). Tan to Sui (Biliary Tract and Pancreas) 9: pp. 1459-72
  23. Hruban, RH, Adsay, NV, Albores-Saavedra, J, Compton, C, Garrett, E, Goodman, SN (2001) Pancreatic intraepithelial neoplasia: a new nomenclature and classification system for pancreatic duct lesions. Am J Surg Pathol 25: pp. 579-86 CrossRef
  24. Takaori, K, Matsusue, S, Fujikawa, T, Kobashi, Y, Ito, T, Matsuo, Y (1998) Carcinoma in situ of the pancreas associated with localized fibrosis: a clue to early detection of neoplastic lesions arising from pancreatic ducts. Pancreas 17: pp. 102-5 CrossRef
  25. Takaori, K, Kobashi, Y, Matsusue, S, Matsui, K, Yamamoto, T (2003) Clinicopathological features of pancreatic intraepithelial neoplasias and their relationship to intraductal papillary–mucinous tumors. J Hepatobiliary Pancreat Surg 10: pp. 125-36 CrossRef
  26. Kogire, M, Tokuhara, K, Itoh, D, Koshiba, T, Sato, M, Yamanaka, H (2003) Atypical ductal hyperplasia of the pancreas associated with a stricture of the main pancreatic duct. J Gastroenterol 38: pp. 295-7 CrossRef
  27. Takaori, K (2003) Dilemma in classifications of possible precursors of pancreatic cancer involving the main pancreatic duct: PanIN or IPMN?. J Gastroenterol 38: pp. 311-3 CrossRef
  28. Hruban, RH, Takaori, K, Klimstra, DS, Adsay, NV, Albores-Saavedra, J, Biankin, AV (2004) An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms. Am J Surg Pathol 28: pp. 977-87 CrossRef
  29. Longnecker, DS, Adler, G, Hruban, RH, Kl?ppel, G Intraductal papillary–mucinous neoplasms of the pancreas. In: Hamilton, SR, Aaltonen, LA eds. (2000) World Health Organization classification of tumours. Pathology and genetics of tumours of the digestive system. IARC, Lyon, pp. 237-40
  30. Lohr, M, Kloppel, G, Maisonneuve, P, Lowenfels, AB, Luttges, J (2005) Frequency of K-ras mutations in pancreatic intraductal neoplasias associated with pancreatic ductal adenocarcinoma and chronic pancreatitis: a meta-analysis. Neoplasia 7: pp. 17-23 CrossRef
  31. Yoshizawa, K, Nagai, H, Sakurai, S, Hironaka, M, Morinaga, S, Saitoh, K (2002) Clonality and K-ras mutation analyses of epithelia in intraductal papillary mucinous tumor and mucinous cystic tumor of the pancreas. Virchows Arch 441: pp. 437-43 CrossRef
  32. Z'graggen, K, Rivera, JA, Corris, PA, Pins, M, Werner, J, Fernandez-del Castillo, C (1997) Prevalence of activating K-ras mutations in the evolutionary stages of neoplasia in intraductal papillary mucinous tumors of the pancreas. Ann Surg 226: pp. 491-8 CrossRef
  33. Sessa, F, Solcia, E, Capella, C (1994) Intraductal 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 patients. Virchows Arch 425: pp. 357-67 CrossRef
  34. Maitra, A, Adsay, NV, Argani, P, Iacobuzio-Donahue, C, De Marzo, A, Cameron, JL (2003) Multicomponent analysis of the pancreatic adenocarcinoma progression model using a pancreatic intraepithelial neoplasia tissue microarray. Mod Pathol 16: pp. 902-12 CrossRef
  35. Kawahira, H, Kobayashi, S, Kaneko, K, Asano, T, Ochiai, T (2000) p53 protein expression in intraductal papillary mucinous tumors (IPMT) of the pancreas as an indicator of tumor malignancy. Hepatogastroenterology 47: pp. 973-7
  36. Wilentz, RE, Iacobuzio-Donahue, CA, Argani, P, McCarthy, DM, Parsons, JL, Yeo, CJ (2000) Loss of expression of Dpc4 in pancreatic intraepithelial neoplasia: evidence that DPC4 inactivation occurs late in neoplastic progression. Cancer Res 60: pp. 2002-6
  37. Iacobuzio-Donahue, CA, Klimstra, DS, Adsay, NV (2000) DPC-4 protein is expressed in virtually all human intraductal papillary mucinous neoplasms of the pancreas: comparison with conventional ductal carcinomas. Am J Pathol 24: pp. 1544-8 CrossRef
  38. Fukushima, N, Mukai, K, Kanai, Y (1997) Intraductal papillary tumors and mucinous cystic tumors of the pancreas: clinicopathologic study of 38 cases. Hum Pathol 28: pp. 1010-7 CrossRef
  39. Kobari, M, Egawa, S, Shibuya, K (1999) Intraductal papillary mucinous tumors of the pancreas comprise 2 clinical subtypes: differences in clinical characteristics and surgical management. Arch Surg 134: pp. 1131-6 CrossRef
  40. Adsay, NV, Conlon, KC, Zee, SY, Brennan, MF, Klimstra, DS (2002) Intraductal papillary–mucinous neoplasms of the pancreas: an analysis of in situ and invasive carcinomas in 28 patients. Cancer 94: pp. 62-77 CrossRef
  41. Furukawa, T, Kloppel, G, Volkan Adsay, N, Albores-Saavedra, J, Fukushima, N, Horii, A (2005) Classification of types of intraductal papillary–mucinous neoplasm of the pancreas: a consensus study. Virchows Arch 447: pp. 794-9 CrossRef
  42. Nakamura, A, Horinouchi, M, Goto, M, Nagata, K, Sakoda, K, Takao, S (2002) New classification of pancreatic intraductal papillary–mucinous tumour by mucin expression: its relationship with potential for malignancy. J Pathol 197: pp. 201-10 CrossRef
  43. Adsay, NV, Adair, CF, Heffess, CS, Klimstra, DS (1996) Intraductal oncocytic papillary neoplasms of the pancreas. Am J Surg Pathol 20: pp. 980-94 CrossRef
  44. Terris, B, Dubois, S, Buisine, MP, Sauvanet, A, Ruszniewski, P, Aubert, JP (2002) Mucin gene expression in intraductal papillary–mucinous pancreatic tumours and related lesions. J Pathol 197: pp. 632-7 CrossRef
  45. Luttges, J, Zamboni, G, Longnecker, D, Kloppel, G (2001) The immunohistochemical mucin expression pattern distinguishes different types of intraductal papillary mucinous neoplasms of the pancreas and determines their relationship to mucinous noncystic carcinoma and ductal adenocarcinoma. Am J Surg Pathol 25: pp. 942-8 CrossRef
  46. Adsay, NV, Merati, K, Basturk, O, Iacobuzio-Donahue, C, Levi, E, Cheng, JD (2004) Pathologically and biologically distinct types of epithelium in intraductal papillary mucinous neoplasms: delineation of an “intestinal-pathway of carcinogenesis in the pancreas. Am J Surg Pathol 28: pp. 839-48 CrossRef
  47. Adsay, NV, Pierson, C, Sarkar, F, Abrams, J, Weaver, D, Conlon, K (2001) Colloid (mucinous noncystic) carcinoma of the pancreas. Am J Surg Pathol 25: pp. 26-42 CrossRef
  48. Adsay, NV, Merati, K, Andea, A, Sarkar, F, Hruban, RH, Wilentz, RE (2002) The 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 carcinogenesis. Mod Pathol 15: pp. 1087-95 CrossRef
  49. Kim, GE, Bae, HI, Park, HU, Kuan, SF, Crawley, SC, Ho, JJ (2002) Aberrant expression of MUC5AC and MUC6 gastric mucins and sialyl Tn antigen in intraepithelial neoplasms of the pancreas. Gastroenterology 123: pp. 1052-60 CrossRef
  50. Gudjonsson, T, Magnusson, MK (2005) Stem cell biology and the cellular pathways of carcinogenesis. APMIS 113: pp. 922-9 CrossRef
  51. Thayer, SP, di Magliano, MP, Heiser, PW, Nielsen, CM, Roberts, DJ, Castillo, CF (2003) Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature 425: pp. 851-6 CrossRef
  52. Prasad, NB, Biankin, AV, Fukushima, N, Maitra, A, Dhara, S, Elkahloun, AG (2005) Gene expression profiles in pancreatic intraepithelial neoplasia reflect the effects of Hedgehog signaling on pancreatic ductal epithelial cells. Cancer Res 65: pp. 1619-26 CrossRef
  53. Miyamoto, Y, Maitra, A, Ghosh, B, Zechner, U, Argani, P, Iacobuzio-Donahue, CA (2003) Notch mediates TGF alpha-induced changes in epithelial differentiation during pancreatic tumorigenesis. Cancer Cell 3: pp. 565-76 CrossRef
  
• 作者单位：Kyoichi Takaori (A1)
  
  A1. Department of General and Gastroenterological Surgery, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka, 569-8686, Japan
  

文摘

Precursors to pancreatic cancer have been investigated for a century. Previous studies have revealed three distinct precursors, i.e. mucinous cystic neoplasm (MCN), intraductal papillary mucinous neoplasm (IPMN), and pancreatic intraepithelial neoplasia (PanIN), harboring identical or similar genetic alterations as does invasive pancreatic carcinoma. The current understanding of precursors to pancreatic cancer can be illustrated by progressive pathways from noninvasive MCN, IPMN, and PanIN toward invasive carcinoma. MCNs consist of ovarian-type stroma and epithelial lining with varying grades of atypia, and are occasionally associated with invasive adenocarcinoma. The epithelium of noninvasive IPMNs shows a variety of different directions of differentiation, including gastric, intestinal, pancreatobiliary (PB), and oncocytic types. IPMNs can also harbor varying grades of architectural and cytologic atypia. IPMNs confined to branch ducts are mostly the gastric type, and IPMNs involving the main ducts are often intestinal type, while PB and oncocytic types are rare. Small (<1?cm) IPMNs of the gastric type are not always morphologically distinguishable from low-grade PanINs. Mucin expression profiles suggest intestinal-type IPMNs progress to mucinous noncystic (colloid) carcinoma, while PB-type IPMNs progress toward ductal adenocarcinoma. It is a well-described paradigm that PanIN lesions progress toward ductal adenocarcinoma through step-wise genetic alterations. The activation of Hedgehog and Notch signaling pathways in PanIN lesions as well as in pancreatic adenocarcinoma suggest that developmental pathways may be disregulated during carcinogenesis of the pancreas. Further study is needed to elucidate the pathways from precursors toward invasive carcinoma of the pancreas.