Kalın barsak adenom ve adenokarsinomlarında COX-2, ß-catenin ve p53 ekspresyonu

Year 2020, Volume: 1 Issue: 1, 36 - 46, 01.01.2020

Abdullah Fahri Şahin

Abstract

Kalın barsak kanserleri, tüm dünyada kansere bağlı ölümlerden sorumlu akciğer, meme, prostat tümörlerinden sonra dördüncü kanser türüdür. Besin alışkanlıklarının değişmesi ile birlikte, kanser görülme sıklıkları da artmıştır. Çalışmamıza alınan kalın barsak karsinomlu ve adenoma bulunan vakaların klinik prognostik, histolojik özellikleri ve COX-2, ß-catenin ve p53 ile immünohistokimyasal olarak boyanma özellikleri araştırıldı. Düzce Üniversitesi Tıp Fakültesi Eğitim ve Araştırma Hastanesi Patoloji laboratuarında retrospektif olarak incelenen 77'si adenokarsinom, 42'si adenoma tanısı almış 119 olgu çalışma kapsamına alındı. Adenokarsinomların 36'sı iyi, 25'I orta,16'sı az diferansiye adenokarsinomdu. Adenomların ise 18'I tübülöz, 15'I tübülovillöz, 9'u ise villöz adenomdu. Vakalar WHO'nun derecelendirme ve evreleme sistemine göre sınıflandırıldı. Kalınbarsak kanser ve adenomlarının genel özellikleri, prognostic faktörleri ve COX-2, ß-catenin ve p53 immünoreaktiviteleri incelendi. COX-2 ile boyanma şiddeti ve yüzdesi değerlendirildiğinde; COX-2 ekspresyonunda adanokarsinomlarda adenomlara göre istatistiksel olarak anlamlı bir artış tespit edildi. Benzer şekilde az diferansiye karsinomlarda COX-2'nin boyanma şiddeti ve yüzdesinde istatistiksel olarak anlamlı artış izlendi. Bu nedenle COX-2'yi kötü prognozu gösteren belirteç olarak değerlendirilmiştir. ß-catenin adenokarsinom ve adenomlarda benzer immünoreaktivite gösterdi (p>0.05). Adenokarsinomlarda adenomlara göre p53 ile boyanma yüzdesi istatistiksel olarak anlamlı bir artış izlendi. Bu nedenle p53’de kötü prognozu gösteren bir belirteç olarak değerlendirilmiştir.

Keywords

Kalın barsak karsinomları, adenomlar, COX-2, ß-catenin, p53

Expression of COX-2, ß-catenin and p53 in Colorectal Adenomas and Adenocarcinomas

Abstract

Colorectal carcinoma is fourth common malignant tumor after another major causes of deaths from the malign diseases lung carcinoma, prostat carcinoma and breast carcinoma. Colorectal carcinomas incidence rates increased with hereditary changes. In this study, clinical, prognostic and histological properties of colorectal carcinomas and adenomas were investigated by using immunohistochemical markers COX-2, ßcatenin and p53. In this study, we retrespectively investigated 77 colorectal carcinomas and 42 adenomatous polyps at Department of Pathology, Düzce University Medical School. In our study 36, 25 and 16 adenocarcinomas were well, moderate and poorly differantiated, respectively. Adenomas were grouped as tubular adenoma (n=18), tubulovillous adenoma (n=15), villous adenoma (n=9). Cases were classified according to WHO. General and prognostic features of colorectal carcinomas and adenomas were investigated by applying immunoreactivities, namely COX-2, ß-catenin and p53. In our study, adenocarcinomas were expressed COX-2 more than adenomas. We found that, poorly differentiated adenocarcinomas expressed COX-2 more than well differentiated and moderately differentiated adenocarcinomas. Thus, we tought that COX-2 could be used bad prognostic factor for colorectal carcinomas. ß-catenin was similarly expressed at adenocarcinomas and adenomas. In our study, adenocarcinomas were expressed p53 more than adenomas. We found that, poorly differentiated
adenocarcinomas expressed p53 more than well differentiated and moderately differantiated adenocarcinomas. Thus, we tought that p53 could be used bad prognostic factor for colorectal carcinomas.

Keywords

Colorectal carcinoma, adenoma, COX-2, ß-catenin, p53

References

• 1. Ferlay J. Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012 https://publications.iarc.fr/Databases/Iarc- Cancerbases/GLOBOCAN-2012-Estimated- Cancer-Incidence Mortality-And-Prevalence- Worldwide-In-2012-V1.0-201216.05.2019.
• 2. İlter H, Keskinkılıç B. 2015 yılı Türkiye Kanser İstatistikleri Halk Sağlığı Genel Müdürlüğü Kanser Savaş Daire Başkanlığı, T.C Sağlık Bakanlığı Ankara 2018.
• 3. Wiese FW, Thompson PA, Kadlubar FF. Carcinogen substrate specificity of human COX-1and COX-2. Carcinogenesis. 2001; 22(1): 5-10.
• 4. Plastaras JP, Guengerich FP, Nebert DW, MarnettLJ. Xenobiotic- metabolizing cytochromes P450 convert prostaglandin endoperoxide to hydroxyheptadecatrienoic acid and the mutagen, malondialdehyde. J Biol Chem. 2000; 275(16): 11784-90.
• 5. Washington K, Hamilton K. Expression of beta-catenin and alfacatenin and E-cadherin inbarrett’s esophageal adenocarcinomas. Modpathol 1998; 11(9); 805-13.
• 6. Huiping C, Jonassan JG, et al. Alterations of Ecadherin and beta-catenin in gastic cancers. BMC Cancer 2001; 1:16-30
• 7. Tsuji H, Takahashi H. Nuclear localization of beta-catenin in the hair matrix cells and differantiated keratinocytes. J Dermatol Sci 2001; 27:170-7.
• 8. Moustafa AA, Yen L. Regulation of Ecadherin, beta-catenin complex patterns by epidermal growth factor receptor modulation in human lung cancer cells. Lung Cancer 2002; 37: 49-56
• 9. Zhou YN, Xu CP, Han B. Expression of Ecadherin, beta-catenin in gastic carcinoma and its correlation with the clinicopathological features and patient survival. World J Gatroenterology 2002; 8(6): 987-93.
• 10. Aust DE, Terdiman J, et al. Altered distribution of beta catenin, and its binding proteins Ecadherinand APC, in ulserative colitis releated colorectal cancers. Modpathol. 2001; 14:29-39
• 11. Murata M, Iwao K, Miyoshi Y. Activation of the beta catenin gene by interstitial deletions involving exon 3 as early event in colorectal tumorigenesis. Cancer Letters 2000; 159: 73-8
• 12. Nilbert M, Ramberch E. beta-catenin activation through mutation is rare in rectal cancer. Cancer Genet Cytogenet 2001; 128: 43-45
• 13. Muro G, Munoz J, et al. Prognostic value of the expression of E-cadherin, beta-cateninin bladder cancer. Eur J Cancer 2000; 36: 357-62
• 14. Kumar V, Abbas AK, Fausto N. Neoplasia, chapter7, in Robbins and Cotran Pathologic Basis of Disease, 7th ed. Philadelphia: Elsevier Saunders. 2005: 269-342.
• 15. Seidman JD, Russel P, Kurman RJ. Surface Epithelial Tumors of the Ovary, chapter 18, Blaustein’s Pathology of the Female Genital Tract. Ed Kurman RJ. 5th ed. New York: Springer. 2002: 791-904
• 16. Vojtesek B, Bartek J, Midgley CA, Lane DP. An immünochemical analysis of the human nükleer phosphoprotein P53. J Immunol Methods. 1992; 151(1-2): 237-44
• 17. Vikhanskaya F, D’Incalci M, Broggini M. p73 competes with p53 and attenuates its response in a human ovarian cancer cell line. Nucleic Acids Res. 2000; 28(2): 513-9.
• 18. Wang S, Guo M, Ouyang H, Li X, Cordon-Cardo C. The catalytic subunit of DNA-dependent protein kinase selectively regulates p53- dependent apoptosis but not cell-cycle arrest. Proc Natl Acad Sci U S A. 2000; 97(4): 1584–8.
• 19. Vikhanskaya F, Erba E, D'Incalci M, Broggini M. Introduction of wild-type p53 in a human ovarian cancer cell line not expressing endogenous p53. Nucleic Acids Res 1994; 22(6): 1012-7.
• 20. Azumi N, Czernobilsky B. Immunohistochemistry. Blaustein’s Pathology of the Female Genital Tract. Ed Kurman RJ. 5th ed. New York: Springer. 2002. p:1267.
• 21. Crawford JM, Kumar V: Robbins Temel Patoloji. In Çevikbaş U. Ağız Boşluğu ve Gastrointestinal Sistem. 7.ed, istanbul: Nobel Tıp Kitabevi, 2003: 563-90.
• 22. Pecina-Slaus N. Tumor suppressor gene Ecadherin and its role in normal and malignant cells. Cancer Cell Int 2003; 3: 17-24.
• 23. Rosai J. Surgical Pathology, (9th ed.) China. 2004: 776-855.
• 24. Hamilton Sr, Vogelstein B, Kudo S, Riboli E, Nakamura S, et al. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Digestive System. In: Hamilton SR, Aaltonen LA. Tumours of Colon and Rectum. 1 st ed, Lyon, France: IARC Press; 2000: 103-43.
• 25. Harpaz N, Saxena R: Modern Surgical Pathology. In: Weidner N, Cote RJ, Suster S, Weiss LM. Gastrointestinal Tract, Large Intestine. 1st ed. Saunders, 2003: 749-852
• 26. Harry S. Cooper, Sternberg's Diagnostic Surgical Pathology, (4 th ed.) Philedelphia: Lippincott Williams&Wilkins. 2004: 1543- 602.
• 27. Laakso M, Mutru O, Isomaki H and Koota K. Cancer mortality in patients with rheumotoid arthritis. J. Rheumatol 1986; 13: 522- 26.
• 28. Sheng H, Shao J, Funkhoser EM, Sharp GB. Aspirin and reduced risk of esophageal carcinoma. Cancer (Phila) 1995; 76: 1116-9.
• 29. Laakso M, Mutru O, İsomaki H, KootaA. Cancer mortality in patients with rheumatoid arthritis. J Rheumatol 1986; 13: 522-6
• 30. Thun MJ. Aspirin, NSAIDs and digestive tract cancers. Cancer Metastasis Rev 1994; 13: 269-88
• 31. Sheng H, Shao J, Dixon DA Williams CS, Prescott SM, DuBois RN, Beauchamp RD. Transforming growth factor-beta1 enhances Ha-ras-induced expression of cyclooxygenase-2 in intestinal epithelial cells via stabilization of mRNA. J Biol Chem 2000; 275: 6628-35.
• 32. Washington MK, DuBois RN. Prostaglandin E2 increases growth and motility of colorectal carcinoma cells. J Biol Chem 2001; 276: 18075-81
• 34. Tsujii M, Kawano S, Tsuji S, Sawaoka H, Hori M, DuBois RN. Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 1998; 93: 705-16
• 35. Wendum D, Masliah J, Trugnan G, Flejou JF: Cyclooxygenase-2 and its role in colorectal cancer development. Virchows Arch. 2004; 445: 327-33
• 36. Joo YE, Kim HS, Min SW, Lee WS, Park CH, Park CS, Choi SK, Rew JS, Kim SJ. Expression of cyclooxygenase-2 protein in colorectal carcinomas. Int J Gastrointest Cancer. 2002; 31(1-3): 147-54.
• 37. Brown RS, Wahl RL. Overexpression of Glut- 1 Glucose transporter in human breast cancer. Cancer 1993; 72: 2979-85.
• 38. Schohl A, Fagotto F. β-catenin, MAPK and Smad signaling during early Xenopus development. Development 2001; 129: 37-52.
• 39. Iwamoto M, Ahnen DJ, Franklin WA, Maltzman TH. Experssion of β-catenin and full-length APC protein in nomal and neoplastic colonic tissues. Carcinogenesis 2000; 21: 1935-40.
• 40. Wong SC, Lo ES, Chan AK, Lee KC, Hsiao WL.Nuclear b catenin as a potential prognostic and diagnostic marker in patients with colorectal cancer from Hong Kong. Mol Pathol 2003; 56: 347–52
• 41. Chang H, Su JM, Huang CC, Liu LC, Tsai CH, Chou MC, Lin P. Using a combination of cytochrome P450 1B1 and bcatenin forearly diagnosis and prevention of colorectal cancer. Cancer Detect Prev. 2005; 29(6): 562-9.
• 42. Terry MB, Neugut AI, Mansukhani M, Waye J, Harpaz N, Hibshoosh H. Tobacco, alcohol, and p53 over expression in early colorectal neoplasia. BMC Cancer 2003; 3: 29.
• 43. Shariat SF, Tokunaga H, Zhuo JH. P53, p21, pRb and p16 expression predict clinical outcome in cystectomy with bladder cancer. J Clin Onchol 2004; 22(6): 1014-24.
• 44. Cecilia MP. Lymphoproliferative Disorders of the gastrointestinal tract in Gastrointestinal Pathology Plus: An atlas and text. 3. baskı, 2008.