ÜLSERATİF KOLİTLİ HASTALARIN NON-NEOPLASTİK İNFLAME KOLONİK MUKOZALARINDA MİKROSATELLİT İNSTABİLİTESİ

Yıl 2009, Cilt: 22 Sayı: 1, 12 - 18, 04.05.2015

Özlen Atuğ Mustafa Akkiprik Fatih Eren Arzu Tiftikçi Filiz Türe Özdemir Faruk Aşıcıoğlu Hülya Över Hamzaoğlu Nurdan Tözün

Öz

Giriş ve Amaç: Ülseratif kolit (ÜK), zemininde kanser gelişme riski yüksek olan kronik inflamatuar bir
kolon hastalığıdır. ÜK ile ilişkili kanser gelişimine işaret edecek moleküler bir belirtece ihtiyaç
duyulmaktadır. ÜK ile ilişkili kolorektal kanserlerde DNA tamir mekanizmasındaki yetersizliğin ve genomik
mutasyonların bir belirteci olan mikrosatellit instabilitesinin (MSİ) varlığı gösterilmiştir. ÜK’te neoplastik ve
şiddetli inflamasyon görülen neoplastik olmayan mukozada MSİ’ni gösteren bazı çalışmalar mevcuttur. Bu
çalışmanın amacı neoplastik olmayan hafif-orta derecede inflame ÜK mukozasında MSİ’nin varlığını
araştırmaktır.
Gereç ve Yöntem: ÜK’li 29 hastanın inflame kolonik mucosa örneklerinde multipleks PCR (polimeraz
zincir reaksiyonu) ile standart 5 adet belirteç (BAT-25, BAT-26, D2S123, D5S346, D17S250) kullanılarak
MSİ’nin varlığı araştırıldı.
Bulgular: ÜK’li hastaların neoplastik olmayan hafif-orta derecede inflame mukozalarında MSİ saptanmadı.
Sonuç: ÜK’te MSİ’ni değerlendirirken mukozadaki inflamasyonun derecesi göz önünde bulundurulmalıdır.

Anahtar Kelimeler

Ülseratif kolit, Mikrosatellit instabilite

Kaynakça

• 1. Lynch DAF, Lobo AJ, Sobala GM, Dixon MF, Axon ATR. Failure of colonoscopic surveillance in ulcerative colitis. Gut 1993; 34: 1075–1080.
• 2. Lakatos L, Mester G, Erdelyi Z, et al. Risk factors for ulcerative colitis-associated colorectal cancer in a Hungarian cohort of patients with ulcerative colitis: Results of a population- based study. Inflamm Bowel Dis 2006; 12: 3: 205-211.
• 3. Taylor BA, Pemberton JH, Carpenter HA, et al. Dysplasia in chronic ulcerative colitis: implications for colonoscopic surveillance. Dis Colon Rectum 1992;35: 950-956.
• 4. Aaltonen LA, Peltomaki P, Leach FS, et al. Clues to the pathogenesis of familial colorectal cancer. Science 1993;260:812-816.
• 5. Thibodeau SN, Bren G, Schaid D. Microsatellite instability in cancer of the proximal colon. Science 1993;260:816-819.
• 6. Søreide K, Slewa A, Stokkeland PJ, et al. Microsatellite instability and DNA ploidy in colorectal cancer: potential implications for patients undergoing systematic surveillance after resection. Cancer 2009;115: 271-782
• 7. D'Errico M, Rinaldis ED, Blasi MF, et al. Genomewide expression profile of sporadic gastric cancers with microsatellite instability. Eur J Cancer 2008; Dec 8. [Epub ahead of print]
• 8. Choi YD, Choi J, Kim JH, et al. Microsatellite instability at a tetranucleotide repeat in type I endometrial carcinoma. J Exp Clin Cancer Res 2008; 31;27(1):88.
• 9. Togni R, Bagla N, Muiesan P, et al. Microsatellite instability in hepatocellular carcinoma in noncirrhotic liver in patients older than 60 years. Hepatol Res 2008; Nov 5. [Epub ahead of print]
• 10. Carpagnano GE, Spanevello A, Carpagnano F, et al. Prognostic value of Exhaled Microsatellite alterations at 3p in NSCLC patients. Lung Cancer 2008; Nov 6. [Epub ahead of print]
• 11. Brentnall TA, Chen R, Lee JG, et al. Microsatellite instability and K-ras mutations associated with pancreatic adenocarcinoma and pancreatitis. Cancer Res 1995;55:4264-4267.
• 12. Brentnall TA, Crispin DA, Bronner M, et al. Microsatellite instability in nonneoplastic mucosa from patients with chronic ulcerative colitis. Cancer Res 1996;56:1237-1240.
• 13. Truelove SC, Witts LJ. Cortisone in ulcerative colitis. Final report on therapeutic trial. Br Med J 1995; 2: 1041-1048.
• 14. Rachmilelewitz D Coated mesalazine ( 5-ASA ) versus sulphasalazine in the treatment of active ulcerative colitis: A randomized trial. BMJ 1989; 298: 82-86.
• 15. Matts SGF. The value of rectal biopsy in the diagnosis of ulcerative colitis. Q J Med 1961;120:393-407.
• 16. Riddell RH, Goldman H, Ransohoff DF, et al. Dysplasia in inflammatory bowel disease: standardized classification with provisional clinical application. Hum Pathol 1983;14: 931-968.
• 17. Semba S, Yokozaki H, Yamamoto S, et al. Microsatellite instability in precancerous lesions and adenocarcinomas of stomach. Cancer 1996;77: 1620–1627.
• 18. Hamamoto T, Yokozaki H, Semba S, et al. Altered microsatellites in incomplete-type intestinal metaplasia adjacent to primary gastric cancers. J Clin Pathol 1997;50: 841–846.
• 19. Meltzer SJ, Yin J, Manin B, et al. Microsatellite instability occurs frequently and in both diploid and aneuploid cell populations of Barrett’s-associated esophageal adenocarcinoma. Cancer Res 1994; 54: 3379–3382.
• 20. Ishitsuka T, Kashiwagi H, Konishi F. Microsatellite instability in inflamed and neoplastic epithelium in ulcerative colitis. J Clin Pathol 2001; 54:526-532.
• 21. Tahara T, Inoue N, Hisamatsu T, et al. Clinical significance of microsatellite instability in the inflamed mucosa for the prediction of colonic neoplasms in patients with ulcerative colitis. J Gastroenterol Hepatol 2005; 20:710-715.
• 22. Løvig T, Andersen SN, Clausen OP, Rognum TO. Microsatellite instability in long-standing ulcerative colitis. Scand J Gastroenterol 2007; 42:586-591.
• 23. Suzuki H, Harpaz N, Tarmin L, et al. Microsatellite instability in ulcerative colitis associated colorectal dysplasias and cancers. Cancer Res 1994;54: 4841- 4844.
• 24. Willenbucher RF, Aust DE, Chang CG, et al. Genomic instability is an early event during the progression pathway of ulcerative colitis related neoplasia. Am J Pathol 1999;154:1825-1830
• 25. Takahashi S, Kojima Y, Kinouchi Y, et al. Microsatellite instability and loss of heterozygosity in the nondysplastic colonic epithelium of ulcerative colitis. J Gastroenterol 2003;38: 734- 739