Uloga hipoksije u razvoju trostruko negativnoga duktalnoga invazivnoga karcinoma dojke

doctoral thesis

• Title (english): Role of hypoxia in the development of triple negative invasive ductal breast carcinoma
• Author: Ilija Alvir
• Mentor: Lidija Beketić-Orešković (mentor); MBZ: 143056
• Committee member: Nada Oršolić (član povjerenstva)
• Committee member: Sonja Levanat (član povjerenstva)
• Committee member: Božena Šarčević (član povjerenstva); MBZ: 87995
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2015, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Universal decimal classification (UDC): 57 - Biological sciences. Physical anthropology. Biodiversity

Abstract

Karcinom dojke najzastupljeniji je tip karcinoma u žena. Brojni tumorski pokazatelji koriste se za praćenje karcinoma dojke: veličina, multicentričnost, histološki tip i gradus, status estrogenskih i progesteronskih receptora (ER i PR), HER2 status, limfovaskularna invazija, pozitivni limfni čvorovi aksile i prisutne udaljene metastaze. Trostruko negativan karcinom dojke (eng. triple negative breast cancer, TNBC) najagresivniji je podtip karcinoma dojke s visokom stopom recidiva i lošijim preživljenjem bolesnica. Tumorska hipoksija važan je pokazatelj prognoze maligne bolesti povezana s agresivnijim rastom, ranijim metastaziranjem i lošim odgovorom tumora na liječenje. U hipoksičnim uvjetima dolazi do pojačane izraženosti p53 i indukcije apoptoze preko Bcl-2. Imunohistokemijskom metodom istraživana je povezanost biljega stanične hipoksije karboanhidraze IX (CAIX), Bcl-2, p53 i Ki-67 s pokazateljima agresivnosti karcinoma. Rezultati pokazuju da je istraživani biljeg hipoksije CAIX u statistički značajnoj pozitivnoj korelaciji s p53 te s biljegom proliferacije Ki-67. Protein p53 u pozitivnoj je korelaciji s veličinom tumora te granično s gradusom. Biljeg apoptoze Bcl-2 nije u korelaciji s ostalim ispitivanim biljezima kao ni s pokazateljima agresivnosti karcinoma. Istraživanje je potvrdilo da TNBC imaju agresivnije ponašanje od samog početka. S obzirom da velika većina TNBC ima izražene biljege hipoksije, neki od tih biljega mogli bi biti dio ciljane terapije.

Abstract (english)

Breast cancer (BC) is the most common type of cancer in women. Numerous tumor indicators are used to monitor BC: size, multicentricity, histological type and grade, status of estrogen and progesterone receptors (ER and PR), HER2 status, lymphovascular invasion, positive axillary lymph nodes and presence of distant metastases. The triple negative breast cancer (triple negative breast cancer, TNBC) is very aggressive subtype of BC with a high rate of recurrence and poor survival. Tumor hypoxia is an important indicator of malignant disease prognosis, associated with aggressive growth, early metastasis and poor response to treatment. In hypoxic conditions an increased expression of p53 occurs along with induction of apoptosis via Bcl-2. Using immunohistochemical methods, we investigated the correlation of expression of cellular hypoxia markers, carbonic anhydrase IX (CAIX), Bcl-2, p53 and Ki-67 with indicators of cancer aggressiveness. The results indicated that investigated hypoxia marker CAIX is in statistically significant positive correlation with both p53 and Ki-67. Only p53 was correlated with any of investigated marker. Apoptotic marker Bcl-2 is more expressed at larger tumors. This study confirmed that TNBC have aggressive behavior from the very beginning. Since the vast majority of TNBC expressed markers of hypoxia maybe some of these markers have potential for development targeted therapies.

• Keywords: karcinom dojke; karboanhidraza IX; p53; Bcl-2; Ki-67
• Keywords (english): breast cancer; carboanhydrase IX; p53; Bcl-2; Ki-67
• Language: croatian
• URN:NBN: urn:nbn:hr:217:683477
• Study programme: Title: Biology; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija (doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Closed access
• Created on: 2017-05-16 11:46:38