Yıl: 2012 Cilt: 28 Sayı: 3 Sayfa Aralığı: 251 - 258 Metin Dili: Türkçe İndeks Tarihi: 29-07-2022

CDX2, COX2 and MUC2 expressions in barrett's esophagus: Can they be useful in determination of the dysplasia?

Öz:
Amaç: Özofagus adenokarsinomları için risk faktörü olan Barrett özofagusunun tanımı değişiklik göstermektedir ve tanı için goblet hücresinin olması gerekliliği tartışmalıdır. Ancak Barrett özofagusunda görülen metaplazinin patofizyolojisi tam olarak anlaşılmamıştır ve metaplazi-displazi geçişinin belirlenmesi için yeni yöntemler araştırılmaktadır. Çalışmamızda, Barrett özofagusunda immünohistokimyasal olarak CDX2, COX2 ve MUC2 ekspresyonu ve bunların intestinal metaplazi veya displazinin erken delili olup olamayacağını araştırmayı amaçladık. Gereç ve Yöntem: Boyanma özellikleri, patolojik olarak Barrett özofagusu tanısı almış 22'sinde displazi izlenen 59 olguda, intestinal metaplazik (goblet hücresi içeren kolumnar epitel), goblet hücresi içermeyen (non-goblet) kolumnar epitel, uzak kolumnar epitel (intestinal metaplastik epitelin uzağındaki non-goblet kolumnar epitel) ve skuamöz epitelde ayrı ayrı değerlendirilmiştir. Sonuçlar istatistiksel olarak Pearson ve Fisher testleri ile karşılaştırılmıştır.Bulgular: İntestinal metaplastik, non-goblet kolumnar, uzak kolumnar ve skuamöz epiteldeki boyanma dağılımları sırasıyla şöyleydi: CDX2 için %76,3; %23,7; %2, %0; COX-2 için %93,2; %47,5; %8; %62,9 ve MUC2 için %93,2; %11,9; %4; %0. CDX2, COX2 ve MUC2 ekspresyonu intestinal metaplastik epitelde uzak yerleşimli ve non-goblet kolumnar epitel ile karşılaştırıldığında daha yüksek idi. Displazi odaklarındaki CDX2, COX2 ve MUC2 ekspresyonu istatistiksel olarak anlamlı şekilde azalmıştı (sırasıyla %18,2, %27,3, %31,9 ve p=0.039, 0.0001, 0.0001). Displazi varlığında, komşu skuamöz epitelde de COX2 ekspresyonu düşük olarak izlendi (p=0.014).Sonuç: Goblet hücresi içeren intestinal tip epitelde CDX2, COX2 ve MUC2 ekspresyonu izlenmektedir. Bu belirteçlerin Barrett özofagusu tanısında kullanımı tartışmalı olmakla birlikte, Barrett özofagusu-displazi sekansındaki fark anlamlı görünmektedir.
Anahtar Kelime: Barrett özefagus Biyopsi MUC2 protein, insan Siklooksijenaz 2 inhibitörleri CDX2 protein, insan İmmünohistokimya

Konular: Cerrahi

Barrett özofagusunda CDX2, COX2 ve MUC2 ekspresyonu: Displazinin belirlenmesinde yardımcı olabilir mi?

Öz:
Objective: The description of Barrett's esophagus which is a risk factor for esophageal adenocarcinoma has differences, and the need of goblet cells for diagnosis is controversial. However, the pathophysiology in the metaplasia seen in Barrett's esophagus is not totally understood and new methods are searched for the assessment of progression to dysplasia. We aimed to search the immunohistochemical expression of CDX2, COX2 and MUC2 in Barrett's esophagus to detect any early evidence of intestinal metaplasia or dysplasia. Material and Method: The staining properties were examined in the intestinal metaplastic (goblet cell-containing columnar epithelium), columnar (non-goblet columnar epithelium), distant columnar (non-goblet columnar epithelium distant from intestinal metaplastic epithelium) and squamous epithelium in 59 pathologically diagnosed Barrett's esophagus, 22 of which having dysplasia. The results were compared statistically with Pearson and Fisher exact tests.Results: The distribution of the staining of intestinal metaplastic, non-goblet columnar distant columnar, and squamous epithelium, respectively were as follows: for CDX2 76.3%, 23.7%, 1.7%, 0%; for COX-2 93.2%, 47.5%, 8%, 62.9%; for MUC2 93.2%, 11.9%, 4% and 0%. The expression of CDX2, COX2 and MUC2 in the intestinal metaplastic epithelium was higher than the expression in distant and non-goblet columnar epithelium. The expression of CDX2, COX2 and MUC2 in the foci of dysplasia decreased significantly (18.2%, 27.3%, 31.9%, and p=0.039, 0.0001, 0.0001, respectively). COX2 expression in squamous epithelium was also lower when the adjacent mucosa has dysplasia (p=0.014).Conclusion: The CDX2, COX2 and MUC2 expressions were seen in the intestinal epithelium having goblet cells. The use of the markers in the diagnosis is controversial but the difference in the Barrett esophagus-dysplasia sequence seems to be meaningful.
Anahtar Kelime: CDX2 protein, human Immunohistochemistry Barrett Esophagus Biopsy MUC2 protein, human Cyclooxygenase 2 Inhibitors

Konular: Cerrahi
Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • 1) Fenoglio C: Gastrointestinal Pathology, an atlas and text. 3rd ed., Philadelphia, Lippincott Wilkins, 2008, 62-68
  • 2) Odze RD: Update on the diagnosis and treatment of Barrett esophagus and related neoplastic precursor lesions. Arch Pathol Lab Med 2008, 132:1577-1585
  • 3) Riddell RH, Odze RD: Definition of Barrett's esophagus: time for a rethink- Is intestinal metaplasia dead? Am J Gastroenterol 2009, 104:2588-2594
  • 4) Souza RF, Krishnan K, Spechler SJ: Acid, Bile, and CDX: the ABCs of making Barrett's metaplasia. Am J Physiol Gastrointest Liver Physiol 2008, 295:G211-G218
  • 5) Phillips RW, Frierson HF Jr, Moskaluk CA: Cdx2 as a marker of epithelial intestinal differentiation in the esophagus. Am J Surg Pathol 2003, 27:1442-1447
  • 6) Groisman GM, Amar M, Meir A: Expression of the intestinal marker Cdx2 in the columnar-lined esophagus with and without intestinal (Barrett's) metaplasia. Mod Pathol 2004,17:1282-1288
  • 7) Colleypriest BJ, Palmer RM, Ward SG, Tosh D: Cdx genes, inflammation and the pathogenesis of Barrett's metaplasia. Trends in Molecular Medicine 2009,15:313-322
  • 8) Burjonrappa SC, Reddimasu S, Nawaz Z Gao X, Sharma P, Loggie B: Mucin expression profile in Barrett's, dysplasia, adenocarcinoma sequence in the esophagus. Indian J Cancer 2007, 44:1-5
  • 9) Chinyama CN, Marshall RE, Owen WJ, Mason RC, Kothari D, Wilkinson ML, Sanderson JD: Expression of MUC1 and MUC2 mucin gene products in Barrett's metaplasia, dysplasia and adenocarcinoma: an immunopathological study with clinical correlation. Histopathology 1999, 35:517-524
  • 10) Van De Bovenkamp JH, Korteland-Van Male AM, Warson C, Büller HA, Einerhand AW, Ectors NL, Dekker J: Gastric-type mucin and TFF-peptide expression in Barrett's oesophagus is disturbed during increased expression of MUC2. Histopathology 2003, 42:555-565
  • 11) Hu Y, Jones C, Gellersen O, Williams VA, Watson TJ, Peters JH: Pathogenesis of Barrett esophagus deoxycholic acid up-regulates goblet-specific gene MUC2 in concert with CDX2 in human esophageal cells. Arch of Surg 2007, 142:540-545
  • 12) Steininger H, Pfofe DA, Müller H, Haag-Sunjic G, Fratianu V: Expression of CDX2 and MUC2 in Barrett's mucosa. Pathol Res Pract 2005, 201:573-577
  • 13) Brabender J, Marjoram P, Lord RV, Metzger R, Salonga D, Vallböhmer D, Schäfer H, Danenberg KD, Danenberg PV, Selaru FM, Baldus SE, Hölscher AH, Meltzer SJ, Schneider PM: The molecular signature of normal squamous esophageal epithelium identifies the presence of a field effect and can discriminate between patients with Barrett's esophagus and patients with Barrett's-associated adenocarcinoma. Cancer Epidemiol Biomarkers Prev 2005, 14:2113-2117
  • 14) Si J, Fu X, Behar J, Wands J, Beer DG, Souza RF, Spechler SJ, Lambeth D, Cao W: NADPH oxidase NOX5-S mediates acidinduced cyclooxygenase-2 expression via activation of NF-kappa B in Barrett's esophageal adenocarcinoma cells. Biol Chem 2007, 282:16244-16255
  • 15) Song S, Guha S, Liu K, Buttar NS, Bresalier RS: COX-2 induction by unconjugated bile acids involves reactive oxygen species-mediated signalling pathways in Barrett's oesophagus and oesophageal adenocarcinoma. Gut 2007, 56:1512-1521
  • 16) Hahn HP, Blount PL, Ayub K, Das KM, Souza R, Spechler S, Odze RD: Intestinal differentiation in metaplastic, nongoblet columnar epithelium in the esophagus. Am J Surg Pathol 2009, 33:1006-1015
  • 17) Villanacci V, Rossi E, Zambelli C, Galletti A, Cestari R, Missale G, Casa DD, Bassotti G: COX-2, CDX2, and CDC2 immunohistochemical assessment for dysplasia-carcinoma progression in Barrett's esophagus. Dig Liver Dis 2007, 39:305- 311
  • 18) Chaves P, Cruz C, Dias Pereira A, Suspiro A, de Almeida JC, Leitão CN, Soares J: Gastric and intestinal differentiation in Barrett's metaplasia and associated adenocarcinoma. Dis Esophagus 2005, 18:383-387
  • 19) Weimann A, Zimmermann M, Gross M, Slevogt H, Rieger A, Morawietz L: CDX2 an LI-Cadherin expression in esophageal mucosa: Use of both markers can facilitate the histologic diagnosis of Barrett's Esophagus and carcinoma. Int J Surg Pathol 2010, 18:330-337
  • 20) Glickman JN, Blount PL, Sanchez CA, Cowan DS, Wongsurawat VJ, Reid BJ, Odze RD: Mucin core polypeptide expression in the progression of neoplasia in Barrett's esophagus. Hum Pathol 2006, 37:1304-1315
  • 21) Möbius C, Stein HJ, Spiess C, Becker I, Feith M, Theisen J, Gais P, Jütting U, Siewert JR: COX2 expression, angiogenesis, proliferation and survival in Barrett's cancer. Eur J Surg Oncol 2005, 31:755-759
  • 22) Majka J, Rembiasz K, Migaczewski M, Budzynski A, Ptak- Belowska A, Pabianczyk R, Urbanczyk K, Zub-Pokrowiecka A, Matlok M, Brzozowski T: Cyclooxygenase-2 (COX2) is the key event in pathophysiology of Barrett's esophagus, lesson from experimental animal model and human subjects. J Physiol Pharmacol 2010, 61:409-418
APA TÜRKMEN ÇETİNASLAN İ, BAŞSÜLLÜ N, URAZ S, YERDEL M, MEMİŞOĞLU R, DOĞUSOY G (2012). CDX2, COX2 and MUC2 expressions in barrett's esophagus: Can they be useful in determination of the dysplasia?. , 251 - 258.
Chicago TÜRKMEN ÇETİNASLAN İlknur,BAŞSÜLLÜ NURAY,URAZ Süleyman,YERDEL Mehmet Ali,MEMİŞOĞLU Reşat,DOĞUSOY Gülen BÜLBÜL CDX2, COX2 and MUC2 expressions in barrett's esophagus: Can they be useful in determination of the dysplasia?. (2012): 251 - 258.
MLA TÜRKMEN ÇETİNASLAN İlknur,BAŞSÜLLÜ NURAY,URAZ Süleyman,YERDEL Mehmet Ali,MEMİŞOĞLU Reşat,DOĞUSOY Gülen BÜLBÜL CDX2, COX2 and MUC2 expressions in barrett's esophagus: Can they be useful in determination of the dysplasia?. , 2012, ss.251 - 258.
AMA TÜRKMEN ÇETİNASLAN İ,BAŞSÜLLÜ N,URAZ S,YERDEL M,MEMİŞOĞLU R,DOĞUSOY G CDX2, COX2 and MUC2 expressions in barrett's esophagus: Can they be useful in determination of the dysplasia?. . 2012; 251 - 258.
Vancouver TÜRKMEN ÇETİNASLAN İ,BAŞSÜLLÜ N,URAZ S,YERDEL M,MEMİŞOĞLU R,DOĞUSOY G CDX2, COX2 and MUC2 expressions in barrett's esophagus: Can they be useful in determination of the dysplasia?. . 2012; 251 - 258.
IEEE TÜRKMEN ÇETİNASLAN İ,BAŞSÜLLÜ N,URAZ S,YERDEL M,MEMİŞOĞLU R,DOĞUSOY G "CDX2, COX2 and MUC2 expressions in barrett's esophagus: Can they be useful in determination of the dysplasia?." , ss.251 - 258, 2012.
ISNAD TÜRKMEN ÇETİNASLAN, İlknur vd. "CDX2, COX2 and MUC2 expressions in barrett's esophagus: Can they be useful in determination of the dysplasia?". (2012), 251-258.
APA TÜRKMEN ÇETİNASLAN İ, BAŞSÜLLÜ N, URAZ S, YERDEL M, MEMİŞOĞLU R, DOĞUSOY G (2012). CDX2, COX2 and MUC2 expressions in barrett's esophagus: Can they be useful in determination of the dysplasia?. Türk Patoloji Dergisi, 28(3), 251 - 258.
Chicago TÜRKMEN ÇETİNASLAN İlknur,BAŞSÜLLÜ NURAY,URAZ Süleyman,YERDEL Mehmet Ali,MEMİŞOĞLU Reşat,DOĞUSOY Gülen BÜLBÜL CDX2, COX2 and MUC2 expressions in barrett's esophagus: Can they be useful in determination of the dysplasia?. Türk Patoloji Dergisi 28, no.3 (2012): 251 - 258.
MLA TÜRKMEN ÇETİNASLAN İlknur,BAŞSÜLLÜ NURAY,URAZ Süleyman,YERDEL Mehmet Ali,MEMİŞOĞLU Reşat,DOĞUSOY Gülen BÜLBÜL CDX2, COX2 and MUC2 expressions in barrett's esophagus: Can they be useful in determination of the dysplasia?. Türk Patoloji Dergisi, vol.28, no.3, 2012, ss.251 - 258.
AMA TÜRKMEN ÇETİNASLAN İ,BAŞSÜLLÜ N,URAZ S,YERDEL M,MEMİŞOĞLU R,DOĞUSOY G CDX2, COX2 and MUC2 expressions in barrett's esophagus: Can they be useful in determination of the dysplasia?. Türk Patoloji Dergisi. 2012; 28(3): 251 - 258.
Vancouver TÜRKMEN ÇETİNASLAN İ,BAŞSÜLLÜ N,URAZ S,YERDEL M,MEMİŞOĞLU R,DOĞUSOY G CDX2, COX2 and MUC2 expressions in barrett's esophagus: Can they be useful in determination of the dysplasia?. Türk Patoloji Dergisi. 2012; 28(3): 251 - 258.
IEEE TÜRKMEN ÇETİNASLAN İ,BAŞSÜLLÜ N,URAZ S,YERDEL M,MEMİŞOĞLU R,DOĞUSOY G "CDX2, COX2 and MUC2 expressions in barrett's esophagus: Can they be useful in determination of the dysplasia?." Türk Patoloji Dergisi, 28, ss.251 - 258, 2012.
ISNAD TÜRKMEN ÇETİNASLAN, İlknur vd. "CDX2, COX2 and MUC2 expressions in barrett's esophagus: Can they be useful in determination of the dysplasia?". Türk Patoloji Dergisi 28/3 (2012), 251-258.