Pancreatic cancer: Molecular biology and early detection

Česká verzia

Authors: A. Ságlová; J. Špičák; T. Hucl
Authors place of work: Přednosta: prof. MUDr. Julius Špičák, CSc. ; Klinika hepatogastroenterologie IKEM
Published in the journal: Prakt. Lék. 2010; 90(8): 489-493
Category: Diagnostis

Summary

Pancreatic cancer is a disease with high malignant potential and is the fourth leading cause of cancer-related death for both men and women. Most patients die within 1 year of diagnosis. It is possible that one out of six cancers occurs in a setting of inherited risk. Like all epithelial malignancies, pancreatic cancer arises by a stepwise progression from non-invasive precursors called PanIN (Pancreatic intraepithelial Neoplasia1, 2, 3), which together with IPMN (Intraductal papillary mucinous Neoplasms) and MCN (Mucinous Cystic Neoplasms) represent lesions with malignant potential. Their histological progression follows genetic progression and some of them can be detected by imaging methods. Identification of patients with hereditary predisposition, early detection of pancreatic cancer precursors and identification of specific molecular alterations to enable rational therapy provide hope for early diagnosis and effective treatment.

Key words:
pancreatic cancer, pathogenesis, screening.

Zdroje

1. Ries, L.A., Eisner, M.P., Kosary, C.L. et al. SEER Cancer Statistics Review, 1973-1996. Bethesda: National Cancer Institute, 2000.

2. Canto, M.I. Strategies for screening for pancreatic adenocarcinoma in high-risk patients. Semin. Oncol. 2007, 34, p. 295-302.

3. Beger, H.G., Rau, B., Gansauge F. et al. Treatment of pancreatic cancer: challenge of the facts. World J. Surg. 2003, 27, p.1075-1084.

4. Almoguera, C., Shibata, D., Forrester, K. et al. Most human carcinomas of the exocrine pankreas contain mutant c-Kras genes. Cell 1988, 53, p. 549-554.

5. Wilentz, R.E., Goggins, M., Redston, M. et al. Genetic, immunohistochemical, and clinical feature sof medullary carcinomas of the pancreas: a newly described and characterized entity. Am. J. Pathol. 2000,156, p. 1641-1651.

6. Pellegata, S., Sessa, F., Renault, B. et al. K-ras and p53 gene mutations in pancreatic cancer: ductal and nonductal tumors progress through different genetic lesions. Cancer Res. 1994, 54, p. 1556-1560.

7. Rozenblum, E., Schutte, M., Goggins, M. et al. Tumor-supressive pathways in pancreatic carcinoma. Cancer Res. 1997, 57, p. 1731-1734.

8. Hahn, S.A., Schutte , M., Hoque, A.T. et al. DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. Science 1996, 271, p. 350-353.

9. Goggins, M., Shekher, M., Turnacioglu, K. et al. Genetic alterations of the TGF beta receptor genes in pancreatic and biliary adenocarcinomas. Cancer Res. 1998, 58, p. 5329-5332.

10. Su, G.H., Bansal, R., Montgomery, E. et al. ACVR1B (ALK4) gene mutations in pancreatic carcinoma. Proc. Natl. Acad. Sci. USA, 2001, 98, p. 3254-3257.

11. Su, G.H., Hruban, R.H., Bansal, R.K. et al. Germline and static mutations of the STK11/LKB1 Peutz-Jeghers gene in pancreatic and biliary cancers. Am. J. Pathol. 1999, 154, p. 1835-1840.

12. Ruggeri, B., Zhang, S.Y., Caamano, J. et al. Human pancreatic carcinomas and cell lines reveal frequent and multiple alterations in the p53 and RB-1 tumor-supressor genes. Oncogene 1992, 7, p. 1503-1511.

13. Su, G.H., Hilgers, W., Shekher, M. et al. Alterations in pancreatic, biliary, and breast carcinomas support MKK4 as a genetically targeted tumor-supressor gene. Cancer Res. 1998, 58, p. 2339-2342.

14. Kern, S.E., Hruban, R.H., Hidalgo, M. et al. An introduction to pancreatic adenocarcinoma genetics, pathology and therapy. Cancer Biol. Ther. 2002, 1, p. 607-613.

15. Calhoun, E.S., Jones, J.B., Ashfaq, R. et al. BRAF and FBXW7 (CDC4, FBW7, AGO, SEL10) mutations in distinct subsets of pancreatic cancer: potential therapeutic targets. Am. J. Pathol. 2003, 163, p. 1255-1260.

16. Hempen, P.M., Kurpad, H., Calhoun, E.S. et al. A double missense variation of the BUB1 gene and a defective mitotic spindle checkpoint in the pancreatic cancer cell line Hs766T. Hum. Mutat. 2003, 21, p. 445.

17. Van der Heijden, M.S., Yeo, C.J., Hruban, R.H. et al. Fanconi anemia gene mutations in young-onset pancreatic cancer. Cancer Res. 2003, 15, p. 2585-2588.

18. Goggins, M., Schutte, M., Lu, J. et al. Germline BRCA2 gene mutations in patients with apparently sporadic pancreatic carcinomas. Cancer Res. 1996, 56, p. 5360-5364.

19. Maitra, A., Kern, S.E., Hruban, R.H. Molecular pathogenesis of pancreatic cancer. Best Pract. Res. Clin. Gastroenterol. 2006, 20, p. 211-226.

20. Wallrapp, C., Muller-Pillasch, F., Solinas-Toldo, S. et al. Characterization of a high copy number amplification at 6q24 in pancreatic cancer identifies c-MYB as a candidate oncogene. Cancer Res. 1997, 57, p. 3135-3139.

21. Ruggeri, B.A., Huang, L., Wood, M. et al. Amplification and overexpression of the AKT2 oncogene in a subset of human pancreatic ductal adenocarcinomas. Mol. Carcinog. 1998, 21, p. 81-86.

22. Abramson, M.A., Jazag, A., van der Zee, J.A. et al. The molecular biology od pancreatic cancer. Gastrointest. Cancer Res. 2007, 1(suppl 2), S7-S12.

23. Van Heek, N.T., Meeker, A.K., Kern, S.E. et al. Telomere shortening is nearly universal in pancreatic intraepithelial neoplasia. Am. J. Pathol. 2002, 161, p. 1541-1547.

24. Caldas, C., Hahn, S.A., Hruban, R.H. et al. Detection of K-ras mutations in the stool of patiens with pancreatic adenocarcinoma and pancreatic ductal hyperplasia. Cancer Res. 1994, 54, p. 3568-3573.

25. Jones, J.B., Song, J.J., Hempen, P.M. et al. Detection of mitochondrial DNA mutations in pancreatic cancer offers a mass-ive advantage over detection of nuclear DNA mutations. Cancer Res. 2001, 61, p. 1299-1304.

26. Vimalachandran, D. Genetics and prevention of pancreatic cancer [on line]. 2004-11. Dostupný z WWW: http://www.medscape.com/viewarticle/ 468132_5.

27. Lynch, H.T., Smyrk, T., Kern, S.E. et al. Familial pancreatic cancer: a review. Semin. Oncol. 1996, 23, p. 251-275.

28. Klein, A.P., Hruban, R.H., Brune, K.A. et al. Familial pancreatic cancer. Cancer J. 2001, 7, p. 266-273.

29. Hucl, T. Molekulární patogeneze karcinomu pankreatu. Čes a Slov Ganstroent. Hepatol. 2009, 63(2), s. 58-64.

30. Lal, G., Lui, G., Schmocker, B. et al. Inherited predisposition to pancreatic adenocarcinoma: role of family history and germ line p16, BRCA1, and BRCA2 mutations. Cancer Res. 2000, 60(2), p. 409-416.

31. Goldstein, A.M., Fraser, M.C., Struewing, J.P. et al. Increased risk of pancreatic cancer in melanoma-prone kindreds with p16INK4 mutations. N. Engl. J. Med. 1995, 333, p. 970-974.

32. Flander, T.Y. Pancreatic adenocarcinoma: epidemiology and genetics. Med. Genet. 1996, 33, p. 889-898.

33. Bartsch, D.K., Sina-Frey, M., Lang, S. et al. CDKN2A germline mutations in familial pancreatic cancer. Ann. Surg. 2002, 236(6), p. 730-737.

34. Giardiello, F.M., Brensinger, J.D., Tersmette, A.C. et al. Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology 2000, 119, p. 1447-1453.

35. Lynch, H.T., Voorhees, G.H., Lanspa, S.J. et al. Pancreatic carcinoma and hereditary nonpolyposis colorectal cancer: a family study. Br. J. Cancer. 1985, 52, p. 271-273.

36. Lowenfels, A.B., Maisonneuve, P., DiMagno, E.P. et al. Hereditary pancreatitis and the risk of pancreatic cancer. International Hereditary Pancreatitis Study Group. J. Natl. Cancer Inst. 1997, 89, p. 442-446.

37. Tersmette, A.C., Petersen, G.M., Offerhaus, G.J. et al. Increased risk od incident pancreatic cancer among first-degree relatives of patient with familial pancreatic cancer. Clin. Cancer Res. 2001, 7(3), p. 738-744.

38. Murphy, K.M., Brune, K.A., Griffin, C. et al. Evaluation of candidate genes MAP2K4, MADH4, ACVR1B, and BRCA2 in familial pancreatic cancer: deleterious BRCA2 mutations in 17 %. Cancer Res. 2002, 62, p. 3789-3793.

39. Hruban, R.H., Adsaz, N.V., Albores-Saavedra, J. et al. Pancreatic intraepithelial neoplasia: A new nomenclature and classification system for pancreatic duct lesions. Am. J. Surg. Pathol. 2001, 25, p. 579-586.

40. Hruban, R.H., Maitra, A., Kern, S.E. et al. Precursors to pancreatic cancer. Gastroenterol. Clin. North. Am. 2007, 36, p. 831-849.

41. Kern, S.E. Advances from genetic clues in pancreatic cancer. Curr. Opin. Onc. 1998, 10, p. 74-80.

42. Hruban, R.H., Wilentz, R., Kern, S.E. Genetic progression in the pancreatic ducts. Am. J. Pathol. 2000, 156, p. 1821-1825.

43. Hruban, R.H., Adsay, N.V., Albores-Saavedra, J. et al. Pancreatic intraepithelial neoplasia: a new nomenclature and classification system for pancreatic duct lesions. Am. J. Surg. Pathol. 2001, 25, p. 579-586.

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

45. Wilentz, R.E., Iacobuzio-Donahue, C.A., Argani, P. et al. Loss of expression of Dpc4 in pancreatic intraepithelial neoplasia: evidence that DPC4 inactivation occurs late in neoplastic progression. Cancer Res. 2000, 60, p. 2002-2005.

46. Sohn, T.A., Yeo, C.J., Cameron, J.L. et al. Intraductal papillary mucinous neoplasms of the pancreas: an updated experience. Ann. Surg. 2004, 239, p. 788-797.

47. Hruban, R.H., Maitra, A., Kern, S.E. et al. Precursors to pancreatic cancer. Gastroenterol. Clin. North. Am. 2007, 36, p. 831-849.

48. Bassi, C., Sarr, M.G., Lillemoe, K.D. et al. Natural history of intraductal papillary mucinous neoplasms (IPMN): current evidence and implications for management. J. Gastrointest. Surg. 2008, 12, p. 645-650.

49. Tanaka, M., Chari, S., Adsay, V. et al. International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas. Pancreatology 2006, 6, p. 17–32.

50. Gold, E.B. Epidemiology of and risk factors for pancreatic cancer. Surg. Clin. North Am. 1995, 75, p. 819-843.

51. Michaud, D.S. Dietary meat, dairy products, fat, and cholesterol and pancreatic cancer risk in a prospective study. Am. J. Epidemiol. 2003, 157, p. 1115-1125.

52. Fuchs, G.S., Colditz, G.A., Stamfer, M.J. et al. A prospective study of cigarette smoking and the risk of pancreatic cancer. Arch. Intern. Med. 1996, 156(19), p. 2255-2260.

53. Lowenfels, A.B., Maisonnevue, P., Whitcomb, D.C. et al. Cigarette smoking as a risk factor of pancreatic patients with hereditary pancreatitis. JAMA 2001, 286(2), p. 169-170.

54. Steinberg, W.M., Barkin, J.S., Bradley, E.L. III. et al. Should patients with a strong family history of pancreatic cancer be screened on a periodic basis for cancer of pancreas? Pancreas 2009. 38(5). p. e137-e150.

55. Chiari, T.S, Leibson, C.L., Rabe, K.G. et al. Pancreatic cancer-associated diabetes mellitus: prevalence and temporal association with diagnosis of cancer. Gastroenterology 2008. 134(1). p. 95-101.

56. Howes, N., Lerch, M.N., Greenhalf, W. et al. Clinical and genetic characteristics of hereditary pancreatitis in Europe. Clin. Gastroenterol. Hepatol. 2004, 2, p. 252-261.

57. McFaul, C., Greenhalf, W., Earl, J. et al. Anticipation in familial pancreatic cancer. Gut 2006, 55, p. 252-258.

58. Kim, J.E., Lee, K.T., Lee, J.K. et al. Clinical usefulness of carbohydrate antigen 19-9 as a screening test for pancreatic cancer in an asymptomatic population. J. Gastroenterol. Hepatol. 2004, 19, p. 182-186.

59. Greenhalf, W., Grocock, C., Harcus, M. et al. Screening of high-risk families for pancreatic cancer. Pancreatology 2009, 9, p. 215-222.

60. Van der Heijden, M.S., Brody, J.R., Dezentje, D.A. et al. In vivo therapeutic responses contingent on Fanconi anemia/BRCA2 status of the tumor. Clin. Cancer Res. 2005; 11, p. 7508-7515.