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Title:Vrednotenje izražanja in napovedna vrednost nekaterih tkivnih molekularnih označevalcev raka prostate
Authors:ID Munda, Miha (Author)
ID Štiblar Martinčič, Draga (Mentor) More about this mentor... New window
ID Hajdinjak, Tine (Comentor)
Files:.pdf DR_Munda_Miha_2013.pdf (5,65 MB)
MD5: 436A44B9E73F99C4D7DC6F1B18F42FD4
PID: 20.500.12556/dkum/c1a392d2-ddb7-4838-ac37-758e934fe60a
 
Language:Slovenian
Work type:Dissertation
Typology:2.08 - Doctoral Dissertation
Organization:MF - Faculty of Medicine
Abstract:Rak prostate je med vsemi rakavimi obolenji pri moških v Sloveniji in v svetu na prvem mestu. Kriteriji, ki so trenutno na razpolago za diagnozo raka prostate, pogosto poteka in izida bolezni ne predvidijo zadovoljivo. Pri odkrivanju in zdravljenju raka prostate so potrebni novi označevalci, ki bi omogočali natančnejšo opredelitev posameznikovega tveganja za nastanek in potek bolezni. Tkivni označevalci, še posebej tisti, ki označujejo apoptozo, proliferacijo in gostoto malih žil, so po našem mnenju eni izmed najpomembnejših, ki bi lahko dali večji vpogled in nova spoznanja o biologiji raka prostate. Korak naprej v ovrednotenju in razumevanju izražanja teh tkivnih označevalcev v raku prostate, bi lahko pripomogel k boljšemu razumevanju razvoja oz. patogeneze te bolezni, pomagal pri izbiri zdravljenja s čimmanj stranskimi učinki, lahko pa bi odprl tudi nova izhodišča v iskanju učinkovitejših terapij. Vzorce raka prostate iz prostatektomije, vklopljene v parafin, smo obarvali z imunohistokemično metodo za prikaz tkivnih označevalcev (p53, Caspase 3, bcl-2, CD105) in rezultate primerjali s podatki o starosti bolnika, vrednosti PSA, oceno po Gleasonu pred in po operaciji, stadijem T, oceno po D'Amicu in ponovitvijo bolezni. Ugotoviti smo želeli povezave med proliferacijsko in apoptotsko aktivnostjo, angiogenezo ter morfološkimi značilnostmi oz. s stopnjo razvitosti tumorja po Gleasonu. Razvili smo matematični model, ki upošteva apoptotsko/proliferacijske značilnosti označevalcev. Vrednosti matematičnega modela smo primerjali z enakimi parametri kakor vrednosti posameznih tkivnih označevalcev. Ugotavljali smo tudi, ali se skupini bolnikov z ocenama po Gleasonu 6 in 7 značilno razlikujeta med seboj. Rezultati raziskave so pokazali, da bi tkivna označevalca p53 in bcl-2 lahko imela napovedno vrednost, če ju izrazimo posamič kot indeks ali v matematičnem modelu. Tudi CD105, izražen kot gostota malih žil, je izkazal tendenco napovedne vrednosti, s katero v matematičnem modelu dopolni rezultate indeksa p53 in bcl-2. Caspase 3 se v tkivu raka prostate slabo izraža in ni povezan z nobenimi klinično pomembnimi vrednostmi. Pokazali smo tudi, da so rezultati boljši, če vrednosti posameznih tkivnih označevalcev integriramo v matematični model, kot če uporabimo označevalce posamič. Skupini bolnikov z oceno po Gleasonu 6 in 7 lahko ločimo tudi po izražanju tkivnih označevalcev in še bolj po vrednostih matematičnega modela. S podrobnejšim opisom izražanja nekaterih tkivnih označevalcev v raku prostate smo prispevali k boljšemu razumevanju biološkega poteka te bolezni tudi na slovenski populaciji. Tkivni označevalci p53, bcl-2, CD105 in še posebej na novo razviti matematični model smo dodali k veliki skupini označevalcev, katerih klinična napovedna vrednost potrebuje potrditev z več raziskavami.
Keywords:imunohistokemija, tkivni označevalci, rak prostate, p53, bcl-2, Caspase 3, CD105, matematični model
Place of publishing:[Maribor
Publisher:M. Munda]
Year of publishing:2012
PID:20.500.12556/DKUM-39356 New window
UDC:616.65-006
COBISS.SI-ID:512247096 New window
NUK URN:URN:SI:UM:DK:8LILZU2Z
Publication date in DKUM:15.01.2013
Views:3363
Downloads:366
Metadata:XML DC-XML DC-RDF
Categories:MF
:
MUNDA, Miha, 2012, Vrednotenje izražanja in napovedna vrednost nekaterih tkivnih molekularnih označevalcev raka prostate [online]. Doctoral dissertation. Maribor : M. Munda. [Accessed 25 March 2025]. Retrieved from: https://dk.um.si/IzpisGradiva.php?lang=eng&id=39356
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Secondary language

Language:English
Title:EVALUATING EXPRESSION AND PREDICTING VALUE OF SOME TISSUE MOLECULAR MARKERS IN PROSTATE CANCER
Abstract:Prostate cancer is the most common cancer among male population in Slovenia and worldwide. Criteria available for diagnosis of prostate cancer often do not sufficiently predict the course and outcome of this disease. Thus new markers are needed at the phase of discovering and curing of the prostate cancer, which would enable more accurate definition of ones risk for the development and the course of the disease. In our opinion, tissue markers, especially those, which mark apoptosis, proliferation and microvessel density, could bring new knowledge to understanding of biology of prostate cancer. Moreover, evaluating and understanding of tissue markers expression in prostate cancer could contribute to better understanding of development and pathogenesis of this disease, in order to choose adequate therapy with minimum side effects, and also could open new perspectives in search for new therapies. The paraffin-embedded prostatectomy specimens were stained according to immunohistochemical protocol for p53, Caspase 3, bcl-2 and CD105. The results of tissue markers expression were correlated with patient’s age, PSA value, Gleason score before and after radical prostatectomy, T stage, D'Amico score and biochemical recurrence. We tried to identify relations between proliferative and apoptotic activity, angiogenesis and morfological characteristics in the terms of Gleason score. A mathematical model was developed, which incorporates tissue markers according to their apoptotic/proliferative characteristics. The model was correlated with clinical data. Further, the most relevant factors which could segregate between groups of patients with Gleason score 6 and 7 were identified. The results of this study showed that p53 and bcl-2 could have a prognostic value incorporated in the mathematical model and also when they are applied alone. CD105, expressed as microvessel density, has shown that it could be a prognostic factor in the mathematical model, where it supplements results of p53 and bcl-2 index. Caspase 3 did not show correlation with relevant clinical data. We also show that the results are better when tissue markers values are incorporated in the mathematical model than when applied alone. Tissue markers and even more, the mathematical model, can differentiate between groups of patients with Gleason scores 6 and 7. With a detailed description of expression of tissue markers in prostate cancer we contributed to better understanding of biological behaviour of this disease in slovenian population. Tissue markers p53, bcl-2, CD105 and the mathematical model obtained, could be added to a big group of markers, whose clinical prognostic value is to be verified on a larger scale of research.
Keywords:immunohistochemistry, tissue markers, prostatic cancer, p53, bcl-2, Caspase 3, CD105, mathematical model


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