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Identification and Analysis of Precursors to Invasive Pancreatic Cancer

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Pancreatic Cancer

Part of the book series: Methods in Molecular Medicine™ ((MIMM,volume 103))

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Abstract

Histologically distinct noninvasive precursor lesions have been recognized in the pancreas for close to a century. The recent development of a consistent reproducible nomenclature and classification system for these lesions has been a major advance in the study of these noninvasive precursors. The “pancreatic intraepithelial neoplasia” or PanIN system was developed at a National Cancer Institutes sponsored think tank in Park City, Utah. Numerous studies have now demonstrated that genetic alterations in cancer-associated genes are more common in higher grade PanIN lesions then they are in lower grade PanIN lesions, and that higher grade PanIN lesions have many of the same genetic alterations that are found in invasive ductal adenocarcinomas of the pancreas. Thus, just as there is a progression in the colorectal of adenomas to invasive adenocarcinoma, so too is there a progression in the pancreas of histologically low-grade PanIN, to high-grade PanIN to invasive ductal adenocarcinoma.

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References

  1. Greenlee, R. T., Hill-Harmon, M. B., Murray, T., and Thun, M. (2001) Cancer Statistics, 2001. CA Cancer J. Clin. 51, 16–36.

    Article  Google Scholar 

  2. Warshaw, A. L. and Castillo, C. F. D. (1992) Pancreatic carcinoma. N. Engl. J. Med. 326, 455–465.

    Article  PubMed  CAS  Google Scholar 

  3. Niederhuber, J. E., Brennan, M. F., and Menck, H. R. (1995) The national cancer data base report on pancreatic cancer. Cancer 76, 1671–1677.

    Article  PubMed  CAS  Google Scholar 

  4. Goggins, M., Canto, M., and Hruban, R. H. (2000) Can we screen high-risk individuals to detect early pancreatic carcinoma? J. Surg. Oncol. 74, 243–248.

    Article  PubMed  CAS  Google Scholar 

  5. Hruban, R. H., Canto, M. I., and Yeo, C. J. (2001) Prevention of pancreatic cancer and strategies for management of familial pancreatic cancer. Dig. Dis. 19, 76–84.

    Article  PubMed  CAS  Google Scholar 

  6. Hruban, R. H., Wilentz, R. E., and Kern, S. E. (2000) Genetic progression in the pancreatic ducts. Am. J. Pathol. 156, 1821–1825.

    Article  PubMed  CAS  Google Scholar 

  7. Hruban, R. H., Wilentz, R. E., Goggins, M., Offerhaus, G. J. A., Yeo, C. J., and Kern, S. E. (1999) Pathology of incipient pancreatic cancer. Ann. Oncol. 10, S9–S11.

    Article  Google Scholar 

  8. McCarthy, D. M., Brat, D. J., Wilentz, R. E., et al. (2001) Pancreatic intraepithelial neoplasia and infiltrating adenocarcinoma: Analysis of progession and recurrence by DPC4 immunohistochemical labeling. Hum. Pathol. 32, 638–642.

    Article  PubMed  CAS  Google Scholar 

  9. Wilentz, R. E., Geradts, J., Maynard, R., et al. (1998) Inactivation of the pl6 (INK4A) tumor-suppressor gene in pancreatic duct lesions: Loss of intranuclear expression. Cancer Res. 58, 4740–4754.

    PubMed  CAS  Google Scholar 

  10. Wilentz, R. E., Iacobuzio-Donahue, C. A., Argani, P., et al. (2000) Loss of expression of Dpc4 in pancreatic intraepithelial neoplasia: Evidence that DPC4 inactivation occurs late in neoplastic progression. Cancer Res. 60, 2002–2006.

    PubMed  CAS  Google Scholar 

  11. Hruban, R. H., Adsay, N. V., Albores-Saavedra, J., et al. (2001) Pancreatic intraepithelial neoplasia (PanIN): A new nomenclature and classification system for pancreatic duct lesions. Am. J. Surg. Pathol. 25, 579–586.

    Article  PubMed  CAS  Google Scholar 

  12. Cubilla, A. L. and Fitzgerald, P. J. (1976) Morphological lesions associated with human primary invasive nonendocrine pancreas cancer. Cancer Res. 36, 2690–2698.

    PubMed  CAS  Google Scholar 

  13. Sohn, T. A., Yeo, C. J., Cameron, J. L., Iacobuzio-Donahue, C. A., Hruban, R. H., and Lillemoe, K. D. (2001) Intraductal papillary mucinous neoplasms of the pancreas: An increasingly recognized clinicopathologic entity. Ann. Surg. 234, 313–321.

    Article  PubMed  CAS  Google Scholar 

  14. Seidel, G., Zahurak, M., Iacobuzio-Donahue, C, et al. (2002) Almost all infiltrating colloid carcinomas of the pancreas and periampullary region arise from in situ papillary neoplasms: A study of 39 cases. Am. J. Surg. Pathol. 26, 56–63.

    Article  PubMed  Google Scholar 

  15. Azar, C., Van de Stadt, J., Rickaert, F., et al. (1996) Intraductal papillary mucinous tumours of the pancreas. Clinical and therapeutic issues in 32 patients. Gut 39, 457–464.

    Article  PubMed  CAS  Google Scholar 

  16. Nagai, E., Ueki, T., Chijiiwa, K., Tanaka, M., and Tsuneyoshi, M. (1995) Intraductal papillary mucinous neoplasms of the pancreas associated with so-called “mucinous ductal ectasia.” Histochemical and immunohistochemical analysis of 29 cases. Am. J. Surg. Pathol. 19, 576–589.

    Article  PubMed  CAS  Google Scholar 

  17. Paal, E., Thompson, L. D., Przygodzki, R. M., Bratthauer, G. L., and Heffess, C. S. (1999) A clinicopathologic and immunohistochemical study of 22 intraductal papillary mucinous neoplasms of the pancreas, with a review of the literature. Mod. Pathol. 12, 518–528.

    PubMed  CAS  Google Scholar 

  18. Z’graggen, K., Rivera, J. A., Compton, C. C., et al. (1997) Prevalence of activating K-ras mutations in the evolutionary stages of neoplasia in intraductal papillary mucinous tumors of the pancreas. Ann. Surg. 226, 491–498.

    Article  CAS  Google Scholar 

  19. Fujii, H., Inagaki, M., Kasai, S., et al. (1997) Genetic progression and heterogeneity in intraductal papillary-mucinous neoplasms of the pancreas. Am. J. Pathol. 151, 1447–1454.

    PubMed  CAS  Google Scholar 

  20. Wilentz, R. E., Albores-Saavedra, J., and Hruban, R. H. (2000) Mucinous cystic neoplasms of the pancreas. Semin. Diagn. Pathol. 17, 31–42.

    PubMed  CAS  Google Scholar 

  21. Wilentz, R. E., Albores-Saavedra, J., Zahurak, M., et al. (1999) Pathologic examination accurately predicts prognosis in mucinous cystic neoplasms of the pancreas. Am. J. Surg. Pathol. 23, 1320–1327.

    Article  PubMed  CAS  Google Scholar 

  22. Moskaluk, C. A., Hruban, R. H., and Kern, S. E. (1997) p16 and K-ras gene mutations in the intraductal precursors of human pancreatic adenocarcinoma. Cancer Res. 57, 2140–2143.

    PubMed  CAS  Google Scholar 

  23. Brat, D. J., Lillemoe, K. D., Yeo, C. J., Warfield, P. B., and Hruban, R. H. (1998) Progression of pancreatic intraductal neoplasias to infiltrating adenocarcinoma of the pancreas. Am. J. Surg. Pathol. 22, 163–169.

    Article  PubMed  CAS  Google Scholar 

  24. Brockie, E., Anand, A., and Albores-Saavedra, J. (1998) Progression of atypical ductal hyperplasia/carcinoma in situ of the pancreas to invasive adenocarcinoma. Ann. Diagn. Pathol. 2, 286–292.

    Article  PubMed  CAS  Google Scholar 

  25. Longnecker, D. S., Adler, G., Hruban, R. H., et al. (2000) Intraductal papillary-mucinous neoplasms of the pancreas, in (Hamilton S. R. and Aaltonen, L. A. eds.), Pathology and Genetics of Tumours of the Digestive System. Lyon: IARC Press, pp. 237–240.

    Google Scholar 

  26. Zamboni, G., Kloppel, G., Hruban, R. H., et al. (2000) Mucinous cystic neoplasms of the pancreas, in (Hamilton, S. R. and Aaltonen, L. A. eds.), Pathology and Genetics of Tumours of the Digestive System. Lyon: IARC Press, pp. 234–236.

    Google Scholar 

  27. Moskaluk, C. A. and Kern, S. E. (1997) Microdissection and polymerase chain reaction amplification of genomic DNA from histological tissue sections. Am. J. Pathol. 150, 1547–1552.

    PubMed  CAS  Google Scholar 

  28. Bonner, R. F., Emmert-Buck, M., Cole, K., et al. (1997) Laser capture microdissection: Molecular analysis of tissue. Science 278, 1481–1483.

    Article  PubMed  CAS  Google Scholar 

  29. Maitra, A., Wistuba, I. I., Virmani, A. K., et al. (1999) Enrichment of epithelial cells for molecular studies. Nat. Med. 5, 459–463.

    Article  PubMed  CAS  Google Scholar 

  30. Wilentz, R. E., Su, G. H., Dai, J. L., et al. (2000) Immunohistochemical labeling for Dpc4 mirrors genetic status in pancreatic: A new marker of DPC4 inactiva-tion. Am. J. Pathol. 156, 37–43.

    Article  PubMed  CAS  Google Scholar 

  31. Iacobuzio-Donahue, C. A., Klimstra, D., Adsay, N. V., et al. (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, 1544–1548.

    Article  CAS  Google Scholar 

  32. Iacobuzio-Donahue, C. A., Wilentz, R. E., Argani, P., et al. (2000) Dpc4 protein in mucinous cystic neoplasms of the pancreas: Frequent loss of expression in invasive carcinomas suggests a role in genetic progression. Am. J. Surg. Pathol. 157, 755–761.

    CAS  Google Scholar 

  33. Kononen, J., Bubendorf, L., Kallioniemi, A., et al. (1998) Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat. Med. 4, 844–857.

    Article  PubMed  CAS  Google Scholar 

  34. Mucci, N. R., Akdas, G., Manely, S., and Rubin, M. A. (2000) Neuroendocrine expression in metastatic prostate cancer: Evaluation of high throughput tissue microarrays to detect heterogeneous protein expression. Hum. Pathol. 31, 406–414.

    Article  PubMed  CAS  Google Scholar 

  35. Kallioniemi, O. P., Wagner, U., Kononen, J., and Sauter, G. (2001) Tissue microarray technology for high-throughput molecular profiling of cancer. Hum. Mol. Genet. 10, 657–662.

    Article  PubMed  CAS  Google Scholar 

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Hruban, R.H., Wilentz, R.E., Maitra, A. (2005). Identification and Analysis of Precursors to Invasive Pancreatic Cancer. In: Su, G.H. (eds) Pancreatic Cancer. Methods in Molecular Medicine™, vol 103. Humana Press. https://doi.org/10.1385/1-59259-780-7:001

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  • DOI: https://doi.org/10.1385/1-59259-780-7:001

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-107-3

  • Online ISBN: 978-1-59259-780-2

  • eBook Packages: Springer Protocols

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