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
Greenlee, R. T., Hill-Harmon, M. B., Murray, T., and Thun, M. (2001) Cancer Statistics, 2001. CA Cancer J. Clin. 51, 16–36.
Warshaw, A. L. and Castillo, C. F. D. (1992) Pancreatic carcinoma. N. Engl. J. Med. 326, 455–465.
Niederhuber, J. E., Brennan, M. F., and Menck, H. R. (1995) The national cancer data base report on pancreatic cancer. Cancer 76, 1671–1677.
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.
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.
Hruban, R. H., Wilentz, R. E., and Kern, S. E. (2000) Genetic progression in the pancreatic ducts. Am. J. Pathol. 156, 1821–1825.
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.
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.
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.
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.
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.
Cubilla, A. L. and Fitzgerald, P. J. (1976) Morphological lesions associated with human primary invasive nonendocrine pancreas cancer. Cancer Res. 36, 2690–2698.
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.
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.
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.
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.
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.
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.
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.
Wilentz, R. E., Albores-Saavedra, J., and Hruban, R. H. (2000) Mucinous cystic neoplasms of the pancreas. Semin. Diagn. Pathol. 17, 31–42.
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.
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.
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.
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.
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.
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.
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.
Bonner, R. F., Emmert-Buck, M., Cole, K., et al. (1997) Laser capture microdissection: Molecular analysis of tissue. Science 278, 1481–1483.
Maitra, A., Wistuba, I. I., Virmani, A. K., et al. (1999) Enrichment of epithelial cells for molecular studies. Nat. Med. 5, 459–463.
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.
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.
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.
Kononen, J., Bubendorf, L., Kallioniemi, A., et al. (1998) Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat. Med. 4, 844–857.
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.
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.
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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
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Print ISBN: 978-1-58829-107-3
Online ISBN: 978-1-59259-780-2
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