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The clinical value of determining the presence of tumor infiltrating lymphocytes in patients with breast cancer

dc.contributor.advisorIvković-Kapicl, Tatjana
dc.contributor.otherTrifunović, Jasna
dc.contributor.otherGudurić, Branimir
dc.contributor.otherRadovanović, Zoran
dc.contributor.otherPopović, Lazar
dc.contributor.otherKnežević-Ušaj, Slavica
dc.creatorKolarov Bjelobrk, Ivana
dc.date.accessioned2016-03-17T12:44:08Z
dc.date.available2016-03-17T12:44:08Z
dc.date.available2020-07-03T13:25:43Z
dc.date.issued2016-03-07
dc.identifier.urihttp://nardus.mpn.gov.rs/handle/123456789/4909
dc.identifier.urihttp://www.cris.uns.ac.rs/DownloadFileServlet/Disertacija144707672662092.pdf?controlNumber=(BISIS)96484&fileName=144707672662092.pdf&id=4554&source=NaRDuS&language=srsr
dc.identifier.urihttp://www.cris.uns.ac.rs/record.jsf?recordId=96484&source=NaRDuS&language=srsr
dc.identifier.urihttp://www.cris.uns.ac.rs/DownloadFileServlet/IzvestajKomisije144707671842285.pdf?controlNumber=(BISIS)96484&fileName=144707671842285.pdf&id=4553&source=NaRDuS&language=srsr
dc.description.abstractUVOD: Glavni problem u lečenju karcinoma dojke je kako na osnovu kliničke klasifikacije i morfoloških osobina tumora predvideti njegovo dalje ponašanje. Vrlo često ni kombinacija standardnih prognostičkih faktora ne daje odgovor o potrebi davanja adjuvantne hemioterapije. U cilju sprovođenja adekvatne dalje terapije karcinoma dojke i otkrivanja agresivnih tipova tumora, a nakon hirurškog lečenja, postoji stalna potreba za pronalaženjem novih pokazatelja pomoću kojih bi se identifikovale bolesnice koje imaju povećan rizik od razvoja relapsa bolesti. CILJEVI: Ciljevi su bili da se utvrdi prisustvo, lokalizacija i distribucija tumor infiltrišućih limfocita, kako ukupnih, tako i CD4+ i CD8+ T limfocita u tumoru dojke, njihova povezanost sa standardnim prognostičkim parametrima, kao i njihov prognostički značaj tj. razlike u nivou infiltracije limfocita u tumoru u odnosu na pojavu relapsa bolesti i dužinu preživljavanja. METOD: Istraživanjem je obuhvaćeno 120 bolesnica sa invazivnim duktalnim karcinomom, sa tumorom lokalizovanim samo u dojci, bez zahvatanja kože i grudnog mišića, sa veličinom tumora do 5 cm, bez udaljenih visceralnih i koštanih metastaza, koje su operisane u Institutu za onkologiju Vojvodine. U istraživanje su uključene bolesnice bez metastaza u limfnim čvorovima pazušne jame i bolesnice sa metastazama u limfnim čvorovima pazušne jame. Istraživanjem nisu obuhvaćene bolesnice koje su primale neoadjuvantnu (preoperativnu) hemioterapiju, kao ni bolesnice sa multifokalnim i multicentričnim tumorima. REZULTATI: Gust limfocitni infiltrat uočen je u 14% tumora dojke, umeren limfocitni infiltrat uočen je u 38%, a oskudan u 43% tumora dojke. Limfocitni infiltrat nije uočen u 5% tumora. Gust infiltrat CD4+ limfocita uočen je u 8% tumora dojke, umeren u 44%, a oskudan u 43% tumora dojke. CD4+ limfociti nisu uočeni u 5% tumora. Gust infiltrat CD8+ limfocita uočen je u 1% tumora dojke, umeren u 23%, a oskudan u 66% tumora dojke. CD8+ limfociti nisu uočeni u 10% tumora. Utvrđena je pozitivna povezanost između nivoa TIL-a i CD4+ limfocita i veličine tumora, histološkog stepena diferentovanosti tumora, prisustva metastaza u limfnim čvorovima pazušne jame, HER-2 statusa, tripl negativnog tumora i relapsa bolesti. Utvrđena je negativna povezanost između nivoa TIL-a i CD4+ limfocita i estrogen i progesteron receptora, kao i godina starosti. Utvrđena je pozitivna povezanost između nivoa CD8+ limfocita i histološkog gradusa tumora, kao i HER-2 statusa. Utvrđena je negativna povezanost između nivoa CD8+ limfocita i estrogen i progesteron receptora, kao i godina starosti. ZAKLJUČAK:Rezultati ovog istraživanja pokazuju povezanost tumor infiltrišućih limfocita i CD4+ limfocita sa brojnim negativnim prognostičkim faktorima, te kraćim vremenom slobodnog intervala bez bolesti, što sve ukazuje na to da su tumor infiltrišući limfociti kao i CD4+ limfociti loš prognostički faktor kod bolesnica sa rakom dojke.sr
dc.description.abstractINTRODUCTION: The main problem in the treatment of breast cancer that based on clinical classification and morphological characteristics of the tumor to predict its future behavior. Very often, not a combination of standard prognostic factors does not answer the need of giving adjuvant chemotherapy. In order to implement adequate further treatment of breast cancer and detection aggressive types of tumor, after surgical treatment, there is a constant need to find new indicators by which we can identify patients who have an increased risk of relapse. OBJECTIVES: The objectives were to determine the presence, localization and distribution of tumor infiltrating lymphocytes, in total, as well as CD4+ and CD8+ T lymphocytes in breast cancer, their correlation with standard prognostic parameters, as well as their prognostic value i.e. differences in the level of infiltration of lymphocytes in a tumor in relation to the occurrence of disease relapse and survival. METHOD: The study included 120 patients with invasive ductal carcinoma, tumor localized only in the breast without involvement of the skin and pectoral muscle, the size of tumors up to 5 cm without distant visceral and bone metastases, which are operated at the Institute of Oncology. The study included patients without metastases in axillary lymph nodes and patients with metastases in axillary lymph nodes. The research not covered by patients receiving neoadjuvant chemotherapy, or patients with multifocal and multicentric tumors. RESULTS: The high amount of lymphocytic infiltrate was observed in the 14% a breast tumor, a moderate amount of lymphocytic infiltrate was observed in 38%, and the low in 43% breast tumors. Lymphocytic infiltrate was not observed in 5% of the tumor. High CD4+ lymphocyte infiltration was observed in 8% of breast, moderate in 44%, and the low in 43% of breast tumors. CD4+ lymphocytes were not observed in 5% tumors. High infiltration of CD8+ lymphocytes was observed in 1% of breast, moderate in 23%, and the low 66% breast tumors. CD8+ lymphocytes have not been observed in 10% tumors. There is a positive correlation between the level of TIL and CD4+ lymphocytes and tumor size, histological grade of tumor differentiation, presence of metastases in axillary lymph nodes, HER-2 status, triple negative tumors and relapses of disease. There was a negative correlation between the level of TIL and CD4+ cell counts and estrogen and progesterone receptors, as well as age. There is a positive correlation between the level of CD8+ cells and histological grade of the tumor, and HER-2 status. There was a negative correlation between the level of CD8+ lymphocytes and estrogen and progesterone receptors, as well as age. CONCLUSION: The results of this study demonstrate the association between tumor infiltrating lymphocytes and CD4+ lymphocytes with a number of negative prognostic factors, and shorter free interval without the disease, all of which indicates that the tumor infiltrating lymphocytes and CD4+ lymphocytes bad prognostic factor in patients with breast cancer.en
dc.languagesr (latin script)
dc.publisherУниверзитет у Новом Саду, Медицински факултетsr
dc.rightsopenAccessen
dc.sourceУниверзитет у Новом Садуsr
dc.subjectkarcinom dojkesr
dc.subjectBreast Neoplasmsen
dc.subjectTumor Infiltratingen
dc.subjectLocalen
dc.subjectCD4-Positive T-Lymphocytesen
dc.subjectCD8-Positive T-Lymphocytesen
dc.subjectPrognosisen
dc.subjectImmunologic Factorsen
dc.subjectNeoplasm Recurrenceen
dc.subjectSurvivalen
dc.subjectNeoplasm Metastasisen
dc.subjectLymphocytesen
dc.subjecttumor-infiltrirajući limfocitisr
dc.subjectCD4-pozitivni T-limfocitisr
dc.subjectCD8-pozitivni T-limfocitisr
dc.subjectprognozasr
dc.subjectimunološki faktorisr
dc.subjectlokalni relaps neoplazmisr
dc.subjectpreživljavanjesr
dc.subjectmetastaze neoplazmisr
dc.titleKlinička vrednost određivanja prisustva tumor infiltrišućih limfocita u bolesnica sa karcinomom dojkesr
dc.titleThe clinical value of determining the presence of tumor infiltrating lymphocytes in patients with breast canceren
dc.typedoctoralThesissr
dc.rights.licenseBY-NC-ND
dcterms.abstractИвковић-Капицл Татјана; Трифуновић Јасна; Гудурић Бранимир; Радовановић Зоран; Поповић Лазар; Кнежевић-Ушај Славица; Коларов Бјелобрк Ивана; Клиничка вредност одређивања присуства тумор инфилтришућих лимфоцита у болесница са карциномом дојке; Клиничка вредност одређивања присуства тумор инфилтришућих лимфоцита у болесница са карциномом дојке;
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/34503/Disertacija535.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/34504/IzvestajKomisije535.pdf


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