nach oben

Digestive Diseases and Sciences

Erschienen in:

01.02.2008 | Original Paper

p53 Mutations are Associated with Dysplasia and Progression of Dysplasia in Patients with Crohn’s Disease

verfasst von: Jeffrey W. Nathanson, Nicole E. Yadron, Jeanne Farnan, Sydney Kinnear, John Hart, David T. Rubin

Erschienen in: Digestive Diseases and Sciences | Ausgabe 2/2008

Einloggen, um Zugang zu erhalten

Abstract

Background: Mutations in the tumor suppressor gene p53 are associated with neoplasia in ulcerative colitis, but little is understood of their significance in Crohn’s disease (CD). Purpose: To explore p53 expression as a marker of neoplasia in CD patients. Methods: This is a retrospective review of CD patients who underwent p53 IHC staining in our center between 1995 and 2003. The p53 status was correlated to the presence and grade of neoplasia at the time of staining and in subsequent follow-up. Results: Fourteen CD patients had p53 assessment: eight were p53 positive and six were p53 negative. Seven of eight p53+ had dysplasia (six LGD, one HGD); one of six p53−had dysplasia (LGD) (P = 0.03). Four p53+ patients with follow-up had persistent dysplasia and two had progression to a higher grade. Three p53− patients with follow-up remained free of dysplasia. Conclusions: This limited study shows that p53 over expression in CD patients is associated with dysplasia that may progress to a higher grade of neoplasia over time.

Ekbom A, Helmick C, Zack M, Adami HO (1990) Ulcerative colitis and colorectal cancer. A population-based study. N Engl J Med 323:1228–1233PubMedCrossRef

Ekbom A, Helmick C, Zack M, Adami HO (1990) Increased risk of large-bowel cancer in Crohn’s disease with colonic involvement. Lancet 336:357–359PubMedCrossRef

Gillen CD, Walmsley RS, Prior P, Andrews HA, Allan RN (1994) Ulcerative colitis and Crohn’s disease: a comparison of the colorectal cancer risk in extensive colitis. Gut 35:1590–1592PubMedCrossRef

Jess T, Gamborg M, Matzen P, Munkholm P, Sorensen TI (2005) Increased risk of intestinal cancer in Crohn’s disease: a meta-analysis of population-based cohort studies. Am J Gastroenterol 100:2724–2729PubMedCrossRef

Sachar DB (1994) Cancer in Crohn’s disease: dispelling the myths. Gut 35:1507–1508PubMedCrossRef

Itzkowitz S (2003) Colon carcinogenesis in inflammatory bowel disease: applying molecular genetics to clinical practice. J Clin Gastroenterol 36:S70–S74 discussion S94–S96PubMedCrossRef

Lane DP (1992) Cancer. p53, guardian of the genome Nature 358:15–16PubMedCrossRef

Hollstein M, Sidransky D, Vogelstein B, Harris CC (1991) p53 mutations in human cancers. Science 253:49–53PubMedCrossRef

Carson DA, Lois A (1995) Cancer progression and p53. Lancet 346:1009–1011PubMedCrossRef

10.

Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Nakamura Y, White R, Smits AM, Bos JL (1988) Genetic alterations during colorectal-tumor development. N Engl J Med 319:525–532PubMedCrossRef

11.

Lashner BA, Bauer WM, Rybicki LA, Goldblum JR (2003) Abnormal p53 immunohistochemistry is associated with an increased colorectal cancer-related mortality in patients with ulcerative colitis. Am J Gastroenterol 98:1423–1427PubMed

12.

Brentnall TA, Crispin DA, Rabinovitch PS, Haggitt RC, Rubin CE, Stevens AC, Burmer GC (1994) Mutations in the p53 gene: an early marker of neoplastic progression in ulcerative colitis. Gastroenterology 107:369–378PubMed

13.

Ajioka Y, Watanabe H, Matsuda K (1995) Over-expression of p53 protein in neoplastic changes in ulcerative colitis: immunohistochemical study. J Gastroenterol 30(Suppl 8):33–35PubMed

14.

Burmer GC, Crispin DA, Kolli VR, Haggitt RC, Kulander BG, Rubin CE, Rabinovitch PS (1991) Frequent loss of a p53 allele in carcinomas and their precursors in ulcerative colitis. Cancer Commun 3:167–172PubMed

15.

Burmer GC, Rabinovitch PS, Haggitt RC, Crispin DA, Brentnall TA, Kolli VR, Stevens AC, Rubin CE (1992) Neoplastic progression in ulcerative colitis: histology, DNA content, and loss of a p53 allele. Gastroenterology 103:1602–1610PubMed

16.

Greenwald BD, Harpaz N, Yin J, Huang Y, Tong Y, Brown VL, McDaniel T, Newkirk C, Resau JH, Meltzer SJ (1992) Loss of heterozygosity affecting the p53, Rb, and mcc/apc tumor suppressor gene loci in dysplastic and cancerous ulcerative colitis. Cancer Res 52:741–745PubMed

17.

Harpaz N, Peck AL, Yin J, Fiel I, Hontanosas M, Tong TR, Laurin JN, Abraham JM, Greenwald BD, Meltzer SJ (1994) p53 protein expression in ulcerative colitis-associated colorectal dysplasia and carcinoma. Hum Pathol 25:1069–1074PubMedCrossRef

18.

Taylor HW, Boyle M, Smith SC, Bustin S, Williams NS (1993) Expression of p53 in colorectal cancer and dysplasia complicating ulcerative colitis. Br J Surg 80:442–444PubMedCrossRef

19.

Yin J, Harpaz N, Tong Y, Huang Y, Laurin J, Greenwald BD, Hontanosas M, Newkirk C, Meltzer SJ (1993) p53 point mutations in dysplastic and cancerous ulcerative colitis lesions. Gastroenterology 104:1633–1639PubMed

20.

Ilyas M, Talbot IC (1995) p53 expression in ulcerative colitis: a longitudinal study. Gut 37:802–804PubMedCrossRef

21.

Holzmann K, Klump B, Borchard F, Hsieh CJ, Kuhn A, Gaco V, Gregor M, Porschen R: (1998) Comparative analysis of histology, DNA content, p53 and Ki-ras mutations in colectomy specimens with long-standing ulcerative colitis. Int J Cancer 76:1–6PubMedCrossRef

22.

Sato A, MacHinami R (1999) p53 immunohistochemistry of ulcerative colitis-associated with dysplasia and carcinoma. Pathol Int 49:858–868PubMedCrossRef

23.

Lashner BA, Shapiro BD, Husain A, Goldblum JR (1999) Evaluation of the usefulness of testing for p53 mutations in colorectal cancer surveillance for ulcerative colitis. Am J Gastroenterol 94:456–462PubMedCrossRef

24.

Warren S, Sommers S (1948) Cicatrizing enteritis (regional enteritis) as a pathologic entity: analysis of one hundred and twenty cases. Am J Pathol 24:475–501PubMed

25.

Persson PG, Karlen P, Bernell O, Leijonmarck CE, Brostrom O, Ahlbom A, Hellers G: (1994) Crohn’s disease and cancer: a population-based cohort study. Gastroenterology 107:1675–1679PubMed

26.

Gillen CD, Andrews HA, Prior P, Allan RN (1994) Crohn’s disease and colorectal cancer. Gut 35:651–655PubMedCrossRef

27.

Gyde SN, Prior P, Macartney JC, Thompson H, Waterhouse JA, Allan RN (1980) Malignancy in Crohn’s disease. Gut 21:1024–1029PubMedCrossRef

28.

Weedon DD, Shorter RG, Ilstrup DM, Huizenga KA, Taylor WF (1973) Crohn’s disease and cancer. N Engl J Med 289:1099–1103PubMedCrossRef

29.

Kilgore SP, Sigel JE, Goldblum JR (2000) Hyperplastic-like mucosal change in Crohn’s disease: an unusual form of dysplasia? Mod Pathol 13:797–801PubMedCrossRef

30.

Koda K, Yoshino G, Honda S, Watanabe F, Sugimura H (2000) Adenocarcinoma of the rectum with various grades of atypia in association with Crohn’s disease: a case report and immunohistochemistry of p53 and Ki-67. Pathol Int 50:318–326PubMedCrossRef

31.

Tiszlavicz L, Kapin M, Varkonyi A, Lorincz A, Bartyik K, Varkonyi T (2001) Adenocarcinoma of the colon developing on the basis of Crohn’s disease in childhood. Eur J Pediatr 160:168–172PubMedCrossRef

32.

Fogt F, Vortmeyer AO, Goldman H, Giordano TJ, Merino MJ, Zhuang Z (1998) Comparison of genetic alterations in colonic adenoma and ulcerative colitis-associated dysplasia and carcinoma. Hum Pathol 29:131–136PubMedCrossRef

33.

Sjoqvist U, Befrits R, Soderlund S, Ost A, Karlen P, Tribukait B, Rubio C, Rutgeerts P, Geboes K, Lofberg R (2005) Colorectal cancer in colonic Crohn’s disease–high frequency of DNA-aneuploidy. Anticancer Res 25:4393–4397PubMed

34.

Lofberg R, Brostrom O, Karlen P, Ost A, Tribukait B (1991) Carcinoma and DNA aneuploidy in Crohn’s colitis–a histological and flow cytometric study. Gut 32:900–9004PubMedCrossRef

35.

Markowitz J, McKinley M, Kahn E, Stiel L, Rosa J, Grancher K, Daum F (1997) Endoscopic screening for dysplasia and mucosal aneuploidy in adolescents and young adults with childhood onset colitis. Am J Gastroenterol 92:2001–2006PubMed

36.

Heinzlmann M, Lang SM, Neynaber S, Reinshagen M, Emmrich J, Stratakis DF, Heldwein W, Wiebecke B, Loeschke K (2002) Screening for p53 and K-ras mutations in whole-gut lavage in chronic inflammatory bowel disease. Eur J Gastroenterol Hepatol 14:1061–1066PubMedCrossRef

37.

Lofberg R, Brostrom O, Karlen P, Ost A, Tribukait B (1992) DNA aneuploidy in ulcerative colitis: reproducibility, topographic distribution, and relation to dysplasia. Gastroenterology 102:1149–1154PubMed

38.

Lindberg JO, Stenling RB, Rutegard JN (1999) DNA aneuploidy as a marker of premalignancy in surveillance of patients with ulcerative colitis. Br J Surg 86:947–950PubMedCrossRef

39.

Befrits R, Hammarberg C, Rubin CE (1994) DNA aneuploidy and histologic dysplasia in long-standing ulcerative colitis: A 10-year follow-up study. Dis Colon Rectum 37:313–320PubMedCrossRef

40.

Rubin CE, Haggitt RC, Burmer GC, Brentnall TA, Stevens AC, Levine DS, Dean PJ, Kimmey M, Perera DR, Rabinovitch PS (1992) DNA aneuploidy in colonic biopsies predicts future development of dysplasia in ulcerative colitis. Gastroenterology 103:1611–1620PubMed

41.

Karlen P, Young E, Brostrom O, Lofberg R, Tribukait B, Ost K, Bodian C, Itzkowitz S (1998) Sialyl-Tn antigen as a marker of colon cancer risk in ulcerative colitis: relation to dysplasia and DNA aneuploidy. Gastroenterology 115:1395–1404PubMedCrossRef

42.

Itzkowitz SH, Young E, Dubois D, Harpaz N, Bodian C, Chen A, Sachar DB (1996) Sialosyl-Tn antigen is prevalent and precedes dysplasia in ulcerative colitis: a retrospective case-control study. Gastroenterology 110:694–704PubMedCrossRef

43.

Agoff SN, Brentnall TA, Crispin DA, Taylor SL, Raaka S, Haggitt RC, Reed MW, Afonina IA, Rabinovitch PS, Stevens AC, Feng Z, Bronner MP (2000) The role of cyclooxygenase 2 in ulcerative colitis-associated neoplasia. Am J Pathol 157:737–745PubMed

44.

Brentnall TA, Crispin DA, Bronner MP, Cherian SP, Hueffed M, Rabinovitch PS, Rubin CE, Haggitt RC, Boland CR (1996) Microsatellite instability in nonneoplastic mucosa from patients with chronic ulcerative colitis. Cancer Res 56:1237–1240PubMed

45.

Heinen CD, Noffsinger AE, Belli J, Straughen J, Fischer J, Groden J, Fenoglio-Preiser CM (1997) Regenerative lesions in ulcerative colitis are characterized by microsatellite mutation. Genes Chromosomes Cancer 19:170–175PubMedCrossRef

46.

Fleisher AS, Esteller M, Harpaz N, Leytin A, Rashid A, Xu Y, Liang J, Stine OC, Yin J, Zou TT, Abraham JM, Kong D, Wilson KT, James SP, Herman JG, Meltzer SJ (2000) Microsatellite instability in inflammatory bowel disease-associated neoplastic lesions is associated with hypermethylation and diminished expression of the DNA mismatch repair gene, hMLH1. Cancer Res 60:4864–4868PubMed

47.

Eaden JA, Mayberry JF (2002) Guidelines for screening and surveillance of asymptomatic colorectal cancer in patients with inflammatory bowel disease. Gut 51 Suppl 5:V10–V12

48.

Itzkowitz SH (1997) Inflammatory bowel disease and cancer. Gastroenterol Clin North Am 26:129–139CrossRef

49.

Vemulapalli R, Lance P (1994) Cancer surveillance in ulcerative colitis: more of the same or progress? Gastroenterology 107:1196–1199PubMed

50.

Lynch DA, Lobo AJ, Sobala GM, Dixon MF, Axon AT (1993) Failure of colonoscopic surveillance in ulcerative colitis. Gut 34:1075–1080PubMedCrossRef

51.

Connell WR, Lennard-Jones JE, Williams CB, Talbot IC, Price AB, Wilkinson KH (1994) Factors affecting the outcome of endoscopic surveillance for cancer in ulcerative colitis. Gastroenterology 107:934–944PubMed

52.

Bernstein CN, Shanahan F, Weinstein WM (1994) Are we telling patients the truth about surveillance colonoscopy in ulcerative colitis? Lancet 343:71–74PubMedCrossRef

53.

van Hogezand RA, Eichhorn RF, Choudry A, Veenendaal RA, Lamers CB (2002) Malignancies in inflammatory bowel disease: fact or fiction? Scand J Gastroenterol Suppl (236):48–53

54.

Munkholm P, Langholz E, Davidsen M, Binder V (1993) Intestinal cancer risk and mortality in patients with Crohn’s disease. Gastroenterology 105:1716–1723PubMed

55.

Bernstein CN, Blanchard JF, Kliewer E, Wajda A (2001) Cancer risk in patients with inflammatory bowel disease: a population-based study. Cancer 91:854–862PubMedCrossRef

56.

Ekbom A, Helmick C, Zack M, Adami HO (1991) Extracolonic malignancies in inflammatory bowel disease. Cancer 67:2015–2019PubMedCrossRef

57.

Gollop JH, Phillips SF, Melton 3rd LJ, Zinsmeister AR (1988) Epidemiologic aspects of Crohn’s disease: a population based study in Olmsted County, Minnesota, 1943–1982. Gut 29:49–56PubMedCrossRef

58.

Petras RE, Mir-Madjlessi SH, Farmer RG (1987) Crohn’s disease and intestinal carcinoma. A report of 11 cases with emphasis on associated epithelial dysplasia. Gastroenterology 93:1307–1314PubMed

59.

Richards ME, Rickert RR, Nance FC (1989) Crohn’s disease-associated carcinoma. A poorly recognized complication of inflammatory bowel disease. Ann Surg 209:764–773PubMedCrossRef

60.

Uesugi H, Mitomi H, Sada M, Takahashi H, Kobayashi K, Igarashi M, Katsumata T, Ihara A, Ohtani Y, Ikeda S, Okayasu I (1999) A case of adenocarcinoma of the small intestine in a Japanese patient with Crohn disease: a report with immunohistochemical and oncogenic analyses. Scand J Gastroenterol 34:1162–1167PubMedCrossRef

Titel: p53 Mutations are Associated with Dysplasia and Progression of Dysplasia in Patients with Crohn’s Disease
verfasst von: Jeffrey W. Nathanson
Nicole E. Yadron
Jeanne Farnan
Sydney Kinnear
John Hart
David T. Rubin
Publikationsdatum: 01.02.2008
Verlag: Springer US
Erschienen in: Digestive Diseases and Sciences / Ausgabe 2/2008
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-007-9886-1

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2008

Influence of E. coli Strain Nissle 1917 (EcN) on Intestinal Gas Dynamics and Abdominal Sensation

Functional Expression of μ-Opioid Receptors in the Human Colon Cancer Cell Line, HT-29, and their Localization in Human Colon

Dilation of Benign Strictures in the Esophagus and Colon with the Polyflex Stent: A Case Series Study

Association between Proton Pump Inhibitor Use and Spontaneous Bacterial Peritonitis

Does Mutation of Hepatitis A Virus Exist in North India?