Title Limfociti Foxp3+ u citološkim razmazima punktata limfnih čvorova i njihova povezanost s prognostičkim čimbenicima u bolesnika oboljelih od limfoma
Title (english) Foxp3+ lymphocytes in cytologic smears of lymph node aspirates and their association with prognostic markers in patients with lymphomas
Author Biljana Jelić Puškarić VIAF: 305732407
Mentor Ika Kardum-Skelin (mentor)
Committee member Igor Aurer (predsjednik povjerenstva)
Committee member Slavko Gašparov (član povjerenstva)
Committee member Mihael Skerlev (član povjerenstva)
Granter University of Zagreb School of Medicine Zagreb
Defense date and country 2020-11-12, Croatia
Scientific / art field, discipline and subdiscipline BIOMEDICINE AND HEALTHCARE Clinical Medical Sciences Clinical Cytology
Universal decimal classification (UDC ) 612 - Physiology
Abstract Važan sastavni dio tumorskog mikrookoliša bolesnika s Hodgkinovim (HL) i ne-Hodgkinovim limfomima (NHL) čine CD4+CD25+ regulatorni limfociti T (Treg), karakterizirani ekspresijom transkripcijskog čimbenika Foxp3. Pojačano nakupljanje Treg limfocita u tumorskom tkivu uočeno je u brojnim solidnim tumorima i hematološkim zloćudnim bolestima, uključujući limfome.
Cilj ovog rada je bio usporediti udio Foxp3 pozitivnih limfocita u punktatima limfnih čvorova bolesnika oboljelih od klasičnog HL i NHL u odnosu na kontrolnu skupinu ispitanika s benignom reaktivnom hiperplazijom. Kod bolesnika s klasičnim HL i NHL također smo ispitivali povezanost udjela Foxp3+ limfocita s prognostičkim čimbenicima značajnim za klinički tijek limfoma (dob, spol, klinički stadij, veličina najvećeg tumora, broj ekstranodalnih sijela, prisutnost B simptoma, koncentracija hemoglobina te aktivnost laktat dehidrogenaze u serumu). U istraživanje je uključeno ukupno 137 ispitanika, 34 ispitanika s reaktivnom hiperplazijom limfatičnih stanica te 103 bolesnika s limfomom. U skupini bolesnika s limfomom bio je 31 bolesnik s klasičnim HL, 66 bolesnika s B-NHL te 6 bolesnika s T-NHL. Bolesnici s B-NHL podijeljeni su u dvije skupine: bolesnici s agresivnim (36 bolesnika) i bolesnici s indolentnim B-NHL (30 bolesnika). Udio imunocitokemijski Foxp3+ limfocita je za sve bolesnike izražen na dva načina: kao postotak Foxp3+ limfocita (broj Foxp3+ limfocita / sve limfatične stanice) te kao omjer postotka Foxp3+ limfocita i postotka CD3+ limfocita (broj Foxp3+ limfocita / limfociti T).
U skupini bolesnika s klasičnim HL nađen je najveći postotak Foxp3+ limfocita, sa statistički značajnom razlikom u odnosu na bolesnike s agresivnim i indolentnim B-NHL. Suprotno očekivanjima, postotak Foxp3+ limfocita u skupini bolesnika s B-NHL bio je niži nego u skupini ispitanika s reaktivnom hiperplazijom. Međutim, kada smo udio Foxp3+ limfocita izrazili kao omjer postotka Foxp3+ limfocita i postotka CD3+ limfocita, nađena je statistički značajno veća vrijednost u skupini bolesnika s indolentnim B-NHL te granično značajno veća vrijednost u skupini bolesnika s agresivnim B-NHL u odnosu na reaktivnu limfocitnu hiperplaziju. U skupini koja je obuhvaćala sve bolesnike s limfomom nađena je povezanost većeg postotka Foxp3+ limfocita s povoljnim prognostičkim čimbenicima, kao što su rani klinički stadij, veličina najvećeg tumora <10 cm te nezahvaćenost ekstranodalnih sijela. U skupini bolesnika s NHL, veći postotak Foxp3+ limfocita također je povezan s povoljnim prognostičkim čimbenicima, kao što su rani klinički stadij i veličina najvećeg tumora <10 cm. Međutim, u skupini bolesnika s klasičnim HL nije nađena statistički značajna povezanost udjela Foxp3+ limfocita niti s jednim ispitivanim prognostičkim čimbenikom.
Abstract (english) CD4+CD25+ T regulatory (Treg) cells constitute important elements of the tumor microenvironment of patients with Hodgkin (HL) and non-Hodgkin lymphoma (NHL), with characteristic expression of the transcription factor Foxp3. Elevated numbers of Treg cells in tumor tissues have been observed in various types of solid organ tumors and hematologic malignancies, including lymphomas.
The aim of this study was to compare the proportion of Foxp3+ lymphocytes in fine needle aspirates of lymph nodes in patients with HL and NHL with a control group with benign reactive hyperplasia. In lymphoma (HL and NHL) patients we also analysed the correlation between the proportion of Foxp3+ lymphocytes and prognostic factors affecting the clinical course of the lymphoma (age, gender, clinical stage, size of the largest tumor, number of extranodal involvement sites, presence of B symptoms, hemoglobin concentration, and serum lactate dehydrogenase activity). The study involved a total of 137 participants, 34 with reactive lymphoid cell hyperplasia and 103 with lymphoma. The lymphoma patients group consisted of 31 patients with classical HL, 66 with B-NHL and six with T-NHL. The B-NHL patients were divided into two groups: patients with aggressive (n=36) and indolent B-NHL (n=30). The proportion of Foxp3+ lymphocytes based on immunocytochemical staining was expressed for all patients in two ways: as a percentage of the Foxp3+ cells (number of Foxp3+ cells / all lymphatic cells) and as a ratio between the percentage of Foxp3+ cells and CD3+ cells (number of Foxp3+ cells / T cells).
The highest percentage of Foxp3+ cells was found in the group of patients with classical HL, with a statistically significant difference in comparison to patients with aggressive and indolent B-NHL. Contrary to expected results, the percentage of Foxp3+ cells found in the group of B-NHL patients was lower than in the group of patients with reactive hyperplasia. However, when the proportion of Foxp3+ lymphocytes was expressed as a ratio between the Foxp3+ cell percentage and CD3+ cell percentage, a statistically significant higher value was found in patients with indolent B-HNL and a borderline significant higher value in patients with aggressive B-HNL in comparison to reactive lymphocytic hyperplasia. In the lymphoma patient group, higher percentage of Foxp3+ cells correlated with favorable prognostic factors, such as early clinical stage, size of the largest tumor <10 cm, and no involvement of extranodal sites. In the group of patients with NHL, increased percentage of Foxp3+ cells also correlated with favorable prognostic factors, such as early clinical stage and size of the largest tumor <10 cm. However, in patients with classical HL there was no statistically significant association between the proportion of Foxp3+ lymphocytes and any of the prognostic factors investigated.
Keywords
Ljudi
Mikrookruženje tumora
T-limfociti
regulatorni
Hiperplazija
Kontrolne grupe
Prognoza
Limfom
Limfom
ne-Hodgkin
Limfociti
Hematološke novotvorine
Limfni čvorovi
Laktat dehidrogenaze
Hemoglobini
Keywords (english)
Humans
Tumor Microenvironment
T-Lymphocytes
Regulatory
Hyperplasia
Control Groups
Prognosis
Lymphoma
Lymphoma
Non-Hodgkin
Lymphocytes
Hematologic Neoplasms
Lymph Nodes
Lactate Dehydrogenases
Hemoglobins
Language croatian
URN:NBN urn:nbn:hr:105:153234
Study programme Title: Biomedicine and Health Sciences Study programme type: university Study level: postgraduate Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
Catalog URL https://katalog.nsk.hr/F/19IT7Y755V1NXQJPHCLYSQGPF6BLAPPF179HQ7FAXXMYBYGMV5-06003?func=find-e&request=Limfociti+Foxp3%2B+u+citolo%C5%A1kim+razmazima+punktata+limfnih+%C4%8Dvorova+i+njihova+povezanost+s+prognosti%C4%8Dkim+%C4%8Dimbenicima+u+bolesnika+oboljelih+od+limfoma&find_scan_code=FIND_NAS&adjacent=N&local_base=MF_WEB&x=43&y=13&filter_code_1=WLN&filter_request_1=&filter_code_2=WYR&filter_request_2=&filter_code_3=WYR&filter_request_3=&filter_code_4=WFM&filter_request_4=
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Created on 2021-03-19 09:34:51