Title IZRAŽENOST GLIKOPROTEINSKOG ANTITIJELA MUC2 I VASKULARNOGA ENDOTELNOG ČIMBENIKA RASTA (VEGF) U SLUZNICI BARRETTOVOG JEDNJAKA
Title (english) EXPRESSION OF MUCIN CORE POLYPEPTIDE MUC 2 AND VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) IN BARRETT’S ESOPHAGUS
Author Melanija Ražov Radas
Mentor Aleksandar Včev (mentor)
Committee member Branko ( Dražen) Dmitrović (Kovač) (predsjednik povjerenstva)
Granter Josip Juraj Strossmayer University of Osijek Faculty of Medicine Osijek Osijek
Defense date and country 2017, Croatia
Scientific / art field, discipline and subdiscipline BIOMEDICINE AND HEALTHCARE Clinical Medical Sciences
Universal decimal classification (UDC ) 61 - Medical sciences
Abstract Cilj istraživanja: Cilj ovog istraživanja je bio utvrditi izražajnost MUC2 i VEGF u tkivu sluznice oboljelih od Barettovog jednjaka, potom kod oboljelih od karcinoma jednjaka, te utvrditi je li izražajnost MUC2 i VEGF-a u sluznici BJ-a korisna u determinaciji displazije. Također smo pokušali utvrditi uzrokuje li postojanje bakterije Helycobacter pylori na zahvaćenoj sluznici povećani rizik od nastanka BJ-a i adenokarcinoma. Barrettov je jednjak prekanceroza čija je pojavnost u suvremenom svijetu u izrazitom porastu. Važnost ove bolesti je u činjenici da se radi o prekancerozi u sekvenci metaplazija-displazija-adenokarcinom. Izražajnost glikoproteina MUC2 i VEGF-a u sluznici Barrettovog jednjaka može se dovesti u vezu s većim rizikom razvoja adenokarcinoma jednjaka. Gotovo 95% bolesnika koji razviju karcinom ezofagogastričnog spoja nisu znali da boluju od BJ-a, te da je evolucija od BJ-a do karcinoma trajala 20 – 30 godina. Materijali i metode: U studiju je uključeno 36 bolesnika sa dijagnozom BJ kratkog segmenta sa intestinalnom metaplazijom i/ili displazijom nakon neuspješnog liječenja inhibitorima protonske pumpe. Dijagnoza je potvrđena patohistološkom analizom, a izražajnost MUC2 i VEGF-a imunohistokemijskom analizom. Rezultati : Provedenim istraživanjem potvrdili smo MUC2 pozitivnost u vrčastim stanicama, te VEGF kao osnovu stvaranja vaskularne mreže u metaplastično promjenjenim stanicama BJ-a. Otkriveno je četvoro bolesnika u ranom stadiju adenokarcinoma jednjaka (svima je učinjena kirurška reekcija), 32 bolesnika sa BE; petoro je imalo uvjete za APK, jedan za RFA, jedan za EMR, a 25 ih je liječeno IPP-om. Nakon provedenog liječenja, u kontrolnoj patohistološkoj i imunohistokemijskoj analizi dokazana je regresija BJ u 25 ispitanika Terapija IPP-om značajno je djelovala na smanjenje VEGF-a između dvaju pregleda, ali nije imala učinka na smanjenje MUC2 koji je bio negativan nakon ablativnih tehnika kao što su RFA i EMR. Na osnovu parametra MUC2 nismo mogli razlikovati ispitanike s CA-om i one s BJ-om. Razlog leži u činjenici da je MUC2 zastupljen u vrčastim stanicama koje se nalaze i kod BJ-a i kod CA-a .Isto se odnosi i na VEGF - na osnovu parametra VEGF-a nismo mogli razlikovati one s CA-om i one s BJ-om. Razlog ovakvom nalazu možemo obrazložiti činjenicom da je prisutnost VEGF-a zabilježena i u BJ i u CA jednjaka. Fisherovim egzaktnim testom usporedili smo izraženost MUC2 između DY pozitivnih i DY negativnih ispitanika, zatim razliku u izraženosti VEGF-a između DY pozitivnih i DY negativnih te razliku u izraženosti HP-a. U sve tri analize između DY pozitivnih i DY negativnih nismo dobili statistički znakovit rezultat. Razlog vjerojatno leži u malom uzorku ispitanika koji su imali pozitivan nalaz displazije. Na osnovu izraženosti bakterije HP na sluznici jednjaka moglo se razlikovati ispitanike s CA i one s BJ-om, pri čemu oni s CA imaju manju izraženost HP-a. Zaključak: MUC 2 pozitivnost je karakteristična za vrčaste stanice Barrettovog jednjaka, ali nije jedini biomarker. VEGF je pokazatelj angiogeneze u mukozi oboljelih od Barrettovog jednjaka, sa i/ili bez IM i DY niskog stupnja. Uloga H Pylori je protektivna na sluznici jednjaka. Ukupno, ova disertacjja upucuje na potrebu češćeg uzimanja bioptičkih uzoraka sa EG spoja i kod ispitanika sa minimalnim endoskopskim promjenama na sluznici, te uz klasičnu patohistološku analizu pokazala se korist u dopuni obrade uvođenjem imunohistokemijske analize MUC2 i VEGF-a, kao pokazatelja mogćeg razvoja karcinoma. Tearpija inhibitorima protonske pumpe je i dalje osnova u liječenju, uz uvođenje i razvoj ablativnih tehnika kao što su APK, RFA , EMR.
Abstract (english) Background: The aim of this study was to determine expression of MUC2 and VEGF in the mucosa tissue in patients with Barrett esophagus, then patients with diagnose of esophageal carcinoma and to determine whether expression of MUC2 and VEGF in the BE mucosa may be useful in determining dysplasia. We also tried to determine whether existence of Helicobacter pylori in affected mucosa caused increased risk for BE and adenocarcinoma. Barrett's esophagus is a precancerous lesion whose appearance in the modern world constantly rise. The importance of this disease is in the fact that precancer sequence have three degree : metaplasia-dysplasia-adenocarcinoma. The expressiveness of the glycoprotein MUC2 and VEGF in the mucosa of Barrett esophagus may be associated with a higher risk of developing esophageal adenocarcinoma. Almost 95% of patients who develop cancer of esophagogastric junction did not know that they suffer from BE , and that the evolution of BE to cancer last 20-30 years. Materialis and methods: The study included 36 patients with diagnose of BE short segments with intestinal metaplasia and / or dysplasia after unsuccessful treatment with proton pump inhibitors. The diagnosis was confirmed by histopathological analysis and the expression of MUC2 and VEGF by immunohistochemistry analysis Results: Study have confirmed the MUC2 positivity of goblet cells, and VEGF as a basis for creation of the vascular network in the metaplastic altered cells of BE. We found four patients in the early stage of esophageal adenocarcinoma (all underwent surgical resection), 32 patients with BE; five of them had conditions for APC, one for the RFA, one for EMR, and 25 of them were treated with PPI's. After the treatment, the control histological and imunohistochemistry analysis confirmed the regression of BE in 25 subjects. Treatment with PPI's substantially had influence in reduction of VEGF between the two views, but had no effect in reducing MUC2, which was negative after ablative techniques such as RFA and EMR. Based on the parameter MUC2 , we could not distinguish subjects with CA from those with BE. The reason lied in the fact that MUC2 was presented in goblet cells of BE and CA. Also, based on the parameter of VEGF, we could not distinguish subjects with CA from those with BE. The reason lied in the fact that the presence of VEGF was presended in BE and in the CA esophagus. With Fisher exact test, we compared the expression of MUC2 between DY positive and DY negative subjects, then the difference in the intensity of VEGF between DY positive and DY negative and the difference in the intensity of HP. In all three analyzes between DY positive and DY negative we did not found a statistically significant diference. The reason probably lied in a small sample of subjects who had a positive finding of dysplasia. Based on severity of bacteria HP in the esophageal mucosa, we could distinguish subject with CA and those with BE, among which those with the CA had a smaller expression of HP. Conclusion: MUC 2 positivity is characteristic for goblet cells of Barrett's esophagus, but not the only biomarker. VEGF is an indicator of angiogenesis in the mucosa of Barrett's esophagus, with / or without an IM and low grade DY. The role of H pylori was protecting to the mucosa of the esophagus. This dissertation indicates for more frequent intake of bioptic samples from the EG junction in patients with minimal endoscopic changes in the mucosa. Classic histopathologic analysis showed the benefit of the additional immunohistochemical analysis of MUC2 and VEGF, as indicators for development of an cancer. Teraphy with proton pump inhibitors is still basic protocol for the treatment, with the introduction and development of ablative techniques such as ASF, RFA, EMR.
Keywords
Barrettov jednjak
glikoprotein MUC2
VEGF (vaskularni endotelni čimbenik rasta)
inhibitor protonske pumpe (IPP).
Keywords (english)
Barrett's oesophagus
Mucin core peptid 2
VEGF (vascular endothelial growth factor)
Proton pump inhibitor (PPI).
Language croatian
URN:NBN urn:nbn:hr:152:676046
Study programme Title: University Postgraduate Study Study programme type: university Study level: postgraduate Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
Type of resource Text
File origin Born digital
Access conditions Open access
Terms of use
Created on 2017-09-20 13:02:20