Title ULOGA GLIKOPROTEINA POVEZANOG S
TUMOROM-72 U RAKU ENDOMETRIJA Title (english) ROLE OF TUMOR-ASOCIATED
GLYCOPROTEIN-72 IN ENDOMETRIAL
CARCINOMA Author Ines Kristofić Mentor Gordana Laškarin (mentor)Mentor Emina Babarović (komentor)Committee member Neda Smiljan Severinski (predsjednik povjerenstva)Committee member Damir Babić (član povjerenstva)Committee member Tamara Gulić (član povjerenstva)Committee member Gordana Laškarin (član povjerenstva)Committee member Emina Babarović (član povjerenstva)Granter University of Rijeka Defense date and country 2020, Croatia Scientific / art field, BIOMEDICINE AND HEALTHCARE Universal decimal classificationUDC ) 618 - Gynaecology. Obstetrics ThesaurusMESH - Medical Subject Headings )
Carcinoma, Endometrioid
immunology
Endometrial Neoplasms
ultrastructure
Endometrial Neoplasms
pathology
Glycoproteins
Keratin-19
Prognosis
Abstract Cilj istraživanja: kvantificirati prisutnost CK (cytokeratin) 19 and TAG-72 (engl. tumor
associated glycoprotein 72) u raku endometrija i usporediti rezultate s imunološkim
svojstvima tumorskog mikrookoliša i kliničko-patološkim prognostičkim čimbenicima.
Material i metode: U istraživanje je uključeno 107 uzoraka endometriodinog raka
endometrija od kojih su izrađeni tkivni mikroareji (eng. Tissue microaray TMA). Metodom
imunohistologije obilježavali smo CK 19, TAG-72, CD68, arginazu-1, iNOS (engl. inducible
nitric oxide synthase) i Apaf-1 (engl. apoptotic protease activating factor 1) te kvantificirali broj
stanica i jačinu obilježavanja. Fluorescentnim mikroskopom analizirali smo polarizaciju
makrofaga [CD68/interleukin (IL)-15, CD68/CC ligand (CCL)2, CD68/arginaza-1,
CD68/CCL22], prostorni međuodnos biljega [CK19/TAG-72, CD68/CD56, CK19/perforin,
CD19/TRAIL (TNF-related apoptosis-inducing ligand)].
Rezultati:U endometrioidnom raku endometrija preko 90% stanica je izražavalo TAG-72 i
CK19. Granularni izražaj TAG-72 pozitivno je korelirao s mucinoznom komponentom. Difuzno
membranski i citoplaznatski izražaj TAG-72 u endometrioidnom raku endometrija s
mucinoznom komponentom pozitivno je korelirao s brojem CD68+ stanica u centru tumora,
dok je kontinuirano membranski izražaj TAG-72 u tumorskim žljezdanim stanicama pozitivno
korelirao s veličinom tumora i histološkim gradusom tumora, a negativno s preživljenjem
bolesnica. U centru tumora i na invazivnoj fronti endometrioidnog raka endometrija s
mucinoznom komponentom CD68+ makrofazi izražavaju TAG-72 i posjeduju arginaza-
1+CCL22+CCL2- i IL-15 fenotip s obilježjima M2 aktivacije. Tkivno uvjetovane CD68+stanice
okružuju rijetke NK stanice siromašne s citolotičkim medijatorom perforinom i apoptotičkom
molekulom TRAIL, a broj nekrotičnih tumorskih CK19+ stanica s perforinom u citoplazmi i broj
Apaf-1+ apoptotičnih stanica je bio vrlo mali. Endometrioidni rak endometrija bez mucinozne
komponente je bio infiltran CD68+ makrofagima, koji nisu izražavali agrinazu-1, CCL22, ali
su stvarali CCL2 i IL- 15 te imali veći udio CD56+ stanica i Apaf-1 pozitivnih apoptotičnih
stanica.
Zaključak: TAG-72 obilno izražen na stanicama endometrioidnog raka endometrija s
mucinoznom komponentom podržava M2 program sazrijevanja makrofaga i osposobljava ih
za podešavanje lokalne tolerogene imunološke reakcije djelovanjem na citotoksični potencijal
stanica NK, što bi moglo podržavati nekontrolirani lokalni rast tumora i skratiti preživljenje
bolesnica.
Abstract (english) Aim of the study: To quantify the presence of CK (cytokeratin) 19 and TAG-72 (tumor associated glycoprotein 72) in endometrial cancer and to compare the results with the immunological properties of the tumor microenvironment and clinical-pathological prognostic factors.
Material and methods: Tissue microarrays (TMA) were built form 107 archival endometriod endometrial cancers. Immunohistology was used to label cytokeratin 19, TAG-72, CD68, arginase-1, iNOS (inducible nitric oxide synthase) and Apaf-1 (apoptotic protease activating factor 1) and to quantify cell number and labeling strength. Fluorescence microscopy was used to analyze the polarization of macrophages [CD68/interleukin (IL)-15, CD68/CC ligand (CCL) 2, CD68/arginase-1, CD68/CCL22], spatial interrelationship of markers [CK19/TAG-72, CD68/CD56, CK19/perforin, CD19/TRAIL (TNF-related apoptosis-inducing ligand)].
Results: Over 90% of cells expressed TAG-72 and CK19. Granular expression of TAG-72 was positively correlated with mucinous component. Diffuse membrane and cytoplasmic expression of TAG-72 in endometrioid endometrial cancer with mucinous component was positively correlated with the number of CD68+ cells in the tumor center; continous membrane expression of TAG-72 in tumor glandular cells was positively correlated with tumor size and histological grade and negatively with the overall survival of patients. In tumor center and invasive front of endometrioid endometrial cancer with mucinous component CD68+ macrophages express TAG-72 and possess arginase-1+CCL22+CCL2- and IL-15 phenotype with M2 activation characteristics. Tissue-mediated CD68+ cells surround NK cells poor in the cytolytic mediator perforin and apoptotic molecule TRAIL, and number of necrotic tumor CK19+ cells with perforin in the cytoplasm and the number of Apaf-1+ aptotic cells were very small. Endometrioid endometrial cancer without a mucinous component was infiltrated with CD68+ macrophages, which did not express agrinase-1, CCL22, but produced CCL2 and IL-15, and had a higher proportion of CD56+ cells and Apaf-1 positive apoptotic cells.
Conclusion: TAG-72 is in abundance expressed in endometrioid endometrial cancer cells with a mucinous component, supports the M2 macrophage maturation program which could support uncontrolled local tumor growth and shorten patient survival.
Keywords
endometrioidni rak endometrija
mucinozna komponenta
polarizacija makrofaga
NK stanice
TAG-72
Keywords (english)
endometrioid endometrial cancer
mucinous component
macrophage polarization
NK cells
TAG-72
Language croatian URN:NBN urn:nbn:hr:184:923347 Promotion 2021 Study programme Title: Biomedicine Postgraduate (doctoral) study programme Type of resource Text File origin Born digital Access conditions Access restricted to students and staff of home institution Terms of use Created on 2021-01-20 13:02:08
