Uloga i značenje telomeraze u raku dojke

Kulić, Ana (2010) Uloga i značenje telomeraze u raku dojke. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Breast cancer is a heterogeneous disease that includes numerous biological entities with specific pathological characteristics and variable biological behavior. In this study we intended to investigate the presence of telomerase activity in malignant and benign breast lesions. Telomerase is a ribonucleoprotein complex. It contains three subunits: catalytic subunit of human telomerase reverse transcriptase, telomerase RNA subunit and protein subunit. Telomerase activity is present in various biological processes like aging, stem cell diseases and malignant growth. We analyzed telomerase activity in 102 breast carcinomas, 20 fibrocystic lesions, 20 fibroadenomas and 20 samples of normal beast tissue. Results obtained by TRAP assay (telomeric repeat amplification protocol) were correlated with various clinicopathologic parameters: patient age, size and histological grade of tumor, axillary lymph node status, steroid receptors, HER-2 status, Ki-67 analysis and Cathepsin D values. We also analyzed relationship between telomerase activity and disease-free survival and relationship with ten-year survival. Telomerase activity was present in 77 breast cancers (75,49%). The analysis of telomerase activity in benign lesions and normal breast tissue was negative. Significant correlation was found between telomerase activity and tumor size, the number of axillary lymph nodes involved, histological grade, Ki-67 analysis, HER-2 status and Cathepsin D values. Negative correlation was found between telomerase activity and status of estrogen receptors. Patients with higher telomerase activity had shorter disease-free survival and shorter ten-year survival than those with lower or negative telomerase activity. No relationship was found between telomerase activity and patient age and progesterone receptor status. Cox regression revealed significant impact of estrogen receptor status and telomerase activity on ten-year survival and disease-free survival. Binary logisitic regression showed significant impact of estrogen receptor status and telomerase activity on ten-year survival and significant impact of estrogen and progesterone status as well as telomerase activity on disease-free survival.

Abstract in Croatian

Rak dojke je heterogena bolest koja obuhvaća brojne biološke entitete sa specifičnim patološkim obilježjima i različitim biološkim ponašanjem. U našem istraživanju željeli smo ispitati prisutnost aktivnosti telomeraze u malignim i benignim bolestima dojke. Telomeraza je ribonukleoproteinski kompleks koji se sastoji od tri podjedinice: katalitičke proteinske podjedinice telomeraza reverzne transkriptaze, telomeraza RNA podjedinice i proteinske podjedinice. Aktivnost telomeraze prisutna je u različitim biološkim procesima kao što su starenje, bolesti matičnih stanica i maligni rast. Analizirali smo aktivnost telomeraze u tkivu 102 karcinoma dojke, 20 fibrocističnih promjena dojke, 20 fibroadenoma i 20 zdravih dojki. Rezultate dobivene TRAP analizom (engl. telomeric repeat amplification protocol) usporedili smo s različitim kliničkopatološkim pokazateljima: dobi bolesnica, veličinom i histološkim gradusom tumora, nalazom limfnih čvorova u pazuhu, vrijednostima steroidnih receptora, HER-2 statusom , nalazom Ki-67 i vrijednostima katepsina D. Također smo analizirali odnos aktivnosti telomeraze i razdoblja do ponovne pojave bolesti, te desetogodišnjeg preživljenja bolesnica s karcinomom dojke. Aktivnost telomeraze bila je prisutna u 77 karcinoma dojke (75,49%), dok je nalaz telomeraze u benignim promjenama i zdravom tkivu bio negativan. Utvrđena je statistički značajna pozitivna povezanost između aktivnosti telomeraze i veličine tumora, broja zahvaćenih limfnih čvorova, histološkog gradusa, Ki-67, HER-2 statusa i vrijednosti katepsina D. Negativna povezanost nađena je između aktivnosti telomeraze i statusa estrogenskih receptora. Utvrđeno je da bolesnice koje imaju višu aktivnost telomeaze imaju kraće razdoblje do ponovne pojave bolesti i kraće desetogodišnje preživljenje u odnosu na bolesnice s nižim ili negativnim vrijednostima. Nije nađena povezanost između aktivnosti telomeraze i dobi bolesnica i statusa progesteronskih receptora. Coxova regresija je pokazala statistički značajan utjecaj koncentracije estrogenskih receptora i aktivnosti telomeraze na desetogodišnje preživljenje i relaps bolesti. Binarna logistička regresija za desetogodišnje preživljenje je pokazala statistički značajan utjecaj koncentracije estrogenskih receptora i aktivnosti telomeraze, a za relaps bolesti statistički značajane koncentracije estrogenskih i progesteronskih receptora, te aktivnosti telomeraze.

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