Diagnosis and treatment of patients with Peutz- Jeghers syndrome

Česká verzia

Authors: E. Kresanová ¹; T. Hlavatý ¹ ; M. Huorka ¹; Z. Homérová ¹; J. Payer ¹; D. Ilenčíková ²
Authors place of work: V. interná klinika LF UK a FNsP, Bratislava ¹; Oddelenie onkologickej genetiky, Národný onkologický ústav, Bratislava ²
Published in the journal: Gastroent Hepatol 2010; 64(2): 14-21
Category: Review Article

Summary

Peutz-Jeghers syndrome is a rare autosomal dominant inherited disease characterized by hamartomatous polyps of the gastrointestinal tract, by mucocutaneous pigmentations and an increased risk of intestinal and extraintestinal tumours. Diagnosis of Peutz-Jeghers syndrome requires mucocutaneous lesions, histological finding of typical hamartomas and genetic analysis. Mutation of gene STK 11, a tumour suppressor gene coding protein serine/threonine kinase 11, is the only known cause of Peutz-Jeghers syndrome. 145 mutations of the gene have been described so far, which is probably the reason for the large phenotypic variability. The treatment strategy is based on regular endoscopic or surgical polypectomy and a special oncological screening programme to prevent severe complications of polyposis and the development of an advanced form of malignancies.

Key words:
phenotype – genotype – hamartomatous polyp – cancer – STK 11/LKB 1 – gene coding serine/threonine kinase – Peutz--Jeghers

Zdroje

1. Douglas Riegert-Johnson DG, Westra WT, Hefferon LM et al. Peutz-Jeghers Syndrome. Familial Cancer Syndromes. 2009; Volume 1.

2. Peutz JLA. Very remarkable case of familial polyposis of mucous membrane of intestinal tract and nasopharynx accompanied by peculiar pigmentations of skin and mucous membrane. Nederl Maandschr Geneesk 1922; 10: 134–146.

3. Touraine H. C.T. Syndrome de Peutz (lentigo-polypose digestive). Annales de dermatologie et de syphilographie. Paris 1945 [cited 5 313].

4. Jeghers H, McKusick KV, Katz KH. Generalized intestinal polyposis and melanin spots of the oral mucosa, lips and digits; a syndrome of diagnostic significance. N Engl Med 1949; 241(26): 1031–1036.

5. Hemminki A, Markie D, Tomlinson I et al. A serine/threonine kinase gene defective in Peutz-Jeghers syndrome. Nature 1998; 391(6663): 184–187.

6. Jenne DE, Reimann H, Nezu W et al. Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nat Genet 1998; 18(1): 38–43.

7. Paroubek E. Familial occurrence of small intestine polyposis with pigmentation of lips (Peutz-Jeghers syndrome). Rozhl Chir 1958; 37(2): 118–129.

8. Amos CI, Keitheri-Cheteri MB, Sabripour M et al. Genotype-phenotype correlations in Peutz-Jeghers syndrome. J Med Genet 2004; 41(5): 327–333.

9. Hinds R, Philp C, Hyer W et al. Complications of childhood Peutz-Jeghers syndrome: implications for pediatric screening. J Pediatr Gastroenterol Nutr 2004; 39(2): 219–220.

10. Young RH, Scully RE. Ovarian sex cord-stromal tumors: recent progress. Int Gynecol Pathol 1982; 1(1): 101–123.

11. Ulbright TM, Amin MB, Young RH. Intratubular large cell hyalinizing sertoli cell neoplasia of the testis: a report of 8 cases of a distinctive lesion of the Peutz-Jeghers syndrome. Am J Surg Pathol 2007; 31(6): 827–835.

12. Rodu B, Martinez MG Jr. Peutz-Jeghers syndrome and cancer. Oral Surg Oral Med Oral Pathol 1984; 58(5): 584–588.

13. Yamada K, Matsukawa A, Hori Y et al. Ultrastructural studies on pigmented macules of Peutz-Jeghers syndrome. J Dermatol 1981; 8(5): 367–377.

14. Nakayama H, Fujii M, Kimura A et al. A solitary Peutz-Jeghers-type hamartomatous polyp of the rectum: report of a case and review of the literature. Jpn J Clin Oncol 1996; 26(4): 273–276.

15. Suzuki S, Hirasaki S, Ikeda F et al. Three cases of Solitary Peutz-Jeghers-type hamartomatous polyp in the duodenum. World J Gastroenterol 2008; 14(6): 944–947.

16. Jancu J. Peutz-Jeghers syndrome. Involvement of the gastrointestinal and upper respiratory tracts. Am Gastroenterol 1971; 56(6): 545–549.

17. Sommerhaug RG, Mason T. Peutz-Jeghers syndrome and ureteral polyposis. JAMA 1970; 211(1): 120–122.

18. Wada K, Tanaka M, Yamaguchi K. Carcinoma and polyps of the gallbladder associated with Peutz-Jeghers syndrome. Dig Dis Sci 1987; 32(8): 943–946.

19. Petersen VC, Sheehan AL, Bryan RL et al. Misplacement of dysplastic epithelium in Peutz-Jeghers Polyps: the ultimate diagnostic pitfall? Am J Surg Pathol 2000; 24(1): 34–39.

20. Bolwell JS, James PD. Peutz-Jeghers syndrome with pseudoinvasion of hamartomatous polyps and multiple epithelial neoplasms. Histopathology 1979; 3(1): 39–50.

21. Ichiyoshi Y, Yao T, Nagasaki S et al. Solitary Peutz-Jeghers type polyp of the duodenum containing a focus of adenocarcinoma. Ital J Gastroenterol 1996; 28(2): 95–97.

22. Giardiello FM, Trimbath D. Peutz-Jeghers syndrome and management recommendations. Clin Gastroenterol Hepatol 2006; 4(4): 408–415.

23. Bartosova Z, Zavodna K, Krivulcik T et al. STK11/LKB1 germline mutations in the first Peutz-Jeghers syndrome patients identified in Slovakia. Neoplasma 2007; 54(2): 101–107.

24. Ušák J, Kružliak T, Ušáková V et al. Peutz- Jeghersov syndróm (PJS) – ochorenie geneticky diagnostikované na prelome 21. storočia. Interná med 2006; 6(11): 627–630.

25. Hernan I, Roig I, Martin B et al. De novo germline mutation in the serine-threonine kinase STK11/LKB1 gene associated with Peutz-Jeghers syndrome. Clin Genet 2004; 66(1): 58–62.

26. Forcet C, Etienne-Manneville S, Gaude H et al. Functional analysis of Peutz-Jeghers mutations reveals that the LKB1 C-terminal region exerts a crucial role in regulating both the AMPK pathway and the cell polarity. Hum Mol Genet 2005; 14(10): 1283–1292.

27. Karuman P, Gozani O, Odze RD et al. The Peutz-Jegher gene product LKB1 is a mediator of p53-dependent cell death. Mol Cell 2001; 7(6): 1307–1319.

28. Tiainen M, Vaahtomeri K, Ylikorkala A et al. Growth arrest by the LKB1 tumor suppressor: induction of p21(WAF1/CIP1). Hum Mol Genet 2002; 11(13): 1497–1504.

29. Aretz S, Stienen D, Uhlhaas S et al. High proportion of large genomic STK11 deletions in Peutz-Jeghers syndrome. Hum Mutat 2005; 26(6): 513–519.

30. Vasovcak P, Krepelova A, Puchmajerova A et al. A novel mutation of PTEN gene in a patient with Cowden syndrome with excessive papillomatosis of the lips, discrete cutaneous lesions, and gastrointestinal polyposis. Eur J Gastroenterol Hepatol 2007; 19(6): 513–517.

31. Puchmajerova A, Vasovcak P, Krepelova A et al. Cowden syndrome. Klin Onkol 2009; 22 Suppl: S56–57.

32. McGarrity TJ, Ward MG, Howett MK. Peutz-Jeghers syndrom. GeneReviews, PUBMed, 2007/5.

33. Finan MC, Ray MK. Gastrointestinal polyposis syndromes. Dermatol Clin 1989; 7(3): 419–434.

34. Boardman LA, Thibodeau SN, Schaid DJ et al. Increased risk for cancer in patients with the Peutz-Jeghers syndrome. Ann Intern Med 1998; 128(11): 896–899.

35. McGarrity T, Amos C. Peutz-Jeghers syndrome: clinicopathology and molecular alterations. Cell Mol Life Sci 2006; 63(18): 2135–2144.

36. Lim W, Olschwang S, Keller JJ et al. Relative frequency and morphology of cancers in STK11 mutation carriers. Gastroenterology 2004; 126(7): 1788–1794.

37. Lim W, Hearle N, Shah B et al. Further observations on LKB1/STK11 status and cancer risk in Peutz-Jeghers syndrome. Br J Cancer 2003; 89(2): 308–313.

38. Hearle N, Schumacher V, Menko FH et al. Frequency and spectrum of cancers in the Peutz-Jeghers syndrome. Clin Cancer Res 2006; 12(10): 3209–3215.

39. Fujiwaki R, Takahashi K, Kitao M. Adenoma malignum of the uterine cervix associated with Peutz-Jeghers syndrome: Int J Gynaecol Obstet 1996; 53(2): 171–172.

40. Tsuruchi N, Tsukamoto N, Kaku T et al. Adenoma malignum of the uterine cervix detected by imaging methods in a patient with Peutz-Jeghers syndrome. Gynecol Oncol 1994; 54(2): 232–236.

41. Dunlop MG. Guidance on gastrointestinal surveillance for hereditary non-polyposis colorectal cancer, familial adenomatous polypolis, juvenile polyposis, and Peutz-Jeghers syndrome. Gut 2002; 51 Suppl 5: V21–27.

42. Bourke B, Broderick A, Bohane T. Peutz-Jeghers syndrome and management recommendations. Clin Gastroenterol Hepatol 2006; 4(12): 1550; author reply 1550.

43. Puchmajerova A, Vasovak P, Krepelova A. Peutz-Jeghers syndrome. Klin Onkol 2009; 22 Suppl: S36–37.

44. Caspari R, von Falkenhausen M, Krautmacher C et al. Comparison of capsule endoscopy and magnetic resonance imaging for the detection of polyps of the small intestine in patients with familial adenomatous polyposis or with Peutz-Jeghers‘ syndrome. Endoscopy 2004; 36(12): 1054–1059.

45. Kopacova M, Tacheci I, Rejchrt S et al. Peutz-Jeghers syndrome: diagnostic and therapeutic approach. World J Gastroenterol 2009; 15(43): 5397–5408.

46. Kopacova M, Bures A, Ferko I et al. Comparison of intraoperative enteroscopy and double-balloon enteroscopy for the diagnosis and treatment of Peutz-Jeghers syndrome. Surg Endosc 2010 Jan 28.

47. Sunada K, Yamamoto H. Double-balloon endoscopy: past, present, and future. J Gastroenterol 2009; 44(1): 1–12.

48. Mensink PB, Haringsma T, Kucharzik C et al. Complications of double balloon enteroscopy: a multicenter survey. Endoscopy 2007; 39(7): 613–615.

49. Oncel M, Remzi FH, Church JM et al. Benefits of ‚clean sweep‘ in Peutz-Jeghers patients. Colorectal Dis 2004; 6(5): 332–335.

50. Giardiello FM, Trimbath JD. Peutz-Jeghers syndrome and management recommendations. Clin Gastroenterol Hepatol 2006; 4(4): 408–415.

51. Canto MI. Strategies for screening for pancreatic adenocarcinoma in high-risk patients. Semin Oncol 2007; 34(4): 295–302.

52. Schmeler KM, Lynch HT, Chen LM et al. Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome. N J Engl Med 2006; 354(3): 261–269.

53. McGarrity TJ, Peiffer LP, Amos CI et al. Overexpression of cyclooxygenase 2 in hamartomatous polyps of Peutz-Jeghers syndrome. Am J Gastroenterol 2003; 98(3): 671–678.

54. Udd L, Katajisto P, Rossi D et al. Suppression of Peutz-Jeghers polyposis by inhibition of cyclooxygenase-2. Gastroenterology 2004; 127(4): 1030–1037.

55. Solomon SD, McMurray JJ, Pfeffer MA et al. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med 2005; 352(11): 1071–1080.

56. Wei C, Amos CI, Zhang N et al. Suppression of Peutz-Jeghers polyposis by targeting mammalian target of rapamycin signaling. Clin Cancer Res 2008; 14(4): 1167–1171.

57. Schumacher V, Vogel T, Leube B et al. STK11 genotyping and cancer risk in Peutz-Jeghers syndrome. J Med Genet 2005; 42(5): 428–435.

58. Salloch H, Reinacher-Schick A, Schulmann K et al. Truncating mutations in Peutz-Jeghers syndrome are associated with more polyps, surgical interventions and cancers. Int J Colorectal Dis 2010; 25(1): p. 97-107.

59. Hearle N, Schumacher V, Menko FH et al. Frequency and spectrum of cancers in the Peutz-Jeghers syndrome. Clin Cancer Res 2006; 12(10): 3209–3215.

60. Mehenni H, Resta N, Guanti G et al. Molecular and clinical characteristics in 46 families affected with Peutz-Jeghers syndrome. Dig Dis Sci 2007; 52(8): 1924–1933.