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doctoral thesis
Fosforilirani receptor HER-2 kao pokazatelj rezistencije karcinoma dojke na terapiju trastuzumabom
Zagreb: University of Zagreb, School of Medicine, 2018. urn:nbn:hr:105:704030
Ramić, Snježana
University of Zagreb
School of Medicine

Institutional repository: Dr Med - University of Zagreb School of Medicine Digital Repository

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Ramić, S. (2018). Fosforilirani receptor HER-2 kao pokazatelj rezistencije karcinoma dojke na terapiju trastuzumabom (Doctoral thesis). Zagreb: University of Zagreb, School of Medicine. Retrieved from https://urn.nsk.hr/urn:nbn:hr:105:704030

Ramić, Snježana. "Fosforilirani receptor HER-2 kao pokazatelj rezistencije karcinoma dojke na terapiju trastuzumabom ." Doctoral thesis, University of Zagreb, School of Medicine, 2018. https://urn.nsk.hr/urn:nbn:hr:105:704030

Ramić, Snježana. "Fosforilirani receptor HER-2 kao pokazatelj rezistencije karcinoma dojke na terapiju trastuzumabom ." Doctoral thesis, University of Zagreb, School of Medicine, 2018. https://urn.nsk.hr/urn:nbn:hr:105:704030

Ramić, S. (2018). 'Fosforilirani receptor HER-2 kao pokazatelj rezistencije karcinoma dojke na terapiju trastuzumabom ', Doctoral thesis, University of Zagreb, School of Medicine, accessed 03 April 2025, https://urn.nsk.hr/urn:nbn:hr:105:704030

Ramić S. Fosforilirani receptor HER-2 kao pokazatelj rezistencije karcinoma dojke na terapiju trastuzumabom [Doctoral thesis]. Zagreb: University of Zagreb, School of Medicine; 2018 [cited 2025 April 03] Available at: https://urn.nsk.hr/urn:nbn:hr:105:704030

S. Ramić, "Fosforilirani receptor HER-2 kao pokazatelj rezistencije karcinoma dojke na terapiju trastuzumabom ", Doctoral thesis, University of Zagreb, School of Medicine, Zagreb, 2018. Available at: https://urn.nsk.hr/urn:nbn:hr:105:704030

Metadata
TitleFosforilirani receptor HER-2 kao pokazatelj rezistencije karcinoma dojke na terapiju trastuzumabom
Title (english)Phosphorylated HER-2 receptor as an indicator of breast cancer resistance to trastuzumab
AuthorSnježana Ramić
MentorFabijan Knežević (mentor)
Committee membernije dostupno (član povjerenstva)
GranterUniversity of Zagreb
School of Medicine
Zagreb
Defense date and country2018-11-20, Croatia
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Clinical Medical Sciences
Universal decimal classification
(UDC)		61 - Medical sciences
Abstract
Oko 20-25% karcinoma dojke ima prekomjerno izražene receptore HER2, što doprinosi agresivnijem ponašanju tumora i lošijem tijeku bolesti. Uvođenjem anti-HER2 terapije primjenom trastuzumaba poboljšan je ishod bolesti i preživljenje bolesnica. Unatoč visokoj specifičnosti trastuzumaba, značajan dio bolesnica ne reagira na terapiju. Receptori HER1, HER2, HER3 i HER4 pripadaju obitelji receptora za epidermalne faktore rasta. Vezanje faktora rasta na receptor aktivira proces dimerizacije članova... More HER obitelji te fosforilaciju na citoplazmatskom dijelu receptora, čime se aktivira signalni put. Naše istraživanje provedeno je na 124 uzoraka HER2 pozitivnih karcinoma dojke s pretpostavkom da fosforilacija HER2 predstavlja pravi biljeg receptorske aktivnosti, a dimerizacija HER2 s ostalim receptorima HER doprinosi pojavi rezistencije na trastuzumab. U istraživanju smo koristili metodu imunohistokemijskog bojenja upotrebom primarnih protutijela na fosforilirani HER2 receptor i ostale receptore HER obitelji te istražili povezanost međusobne izraženosti i korelaciju s pojavom rezistencije/progresije bolesti. Rezultati našeg istraživanja utvrdili su da se receptor HER2 uglavnom nalazi u fosforiliranom stanju (66,2% pHER2+), a pozitivan pHER2 status pokazatelj je dobrog odgovora na terapiju trastuzumabom (P<0,001). Negativan status pHER2 je značajan u HER2 intrinzičkoj skupini gdje je 33,3% bolesnica imalo povrat bolesti. Receptori HER1, HER3 i HER4 su izraženi u 9,7%, 70,2% i 71% HER2 pozitivnih karcinoma, a istovremena izraženost pHER2 i HER3 pokazuje statistički značajnu korelaciju (P=0,013). Bolesnice s negativnim pHER2, a pozitivnim HER3 ili HER4, imale su lošije preživljenje odnosno rezistencija je registrirana u 35,3% karcinoma s pHER2‒/HER3+/HER4+. Na osnovi naših rezultata možemo zaključiti da pozitivan fosforilacijski status HER2 određuje bolesnice koje će imati koristi od terapije trastuzumabom. Negativan status pHER2 upućuje na bolesnice kod kojih bi trebalo odmah uvesti dualnu terapiju, pogotovo u HER2 intrinzičkoj skupini karcinoma dojke. Less
Abstract (english)
About 20-25% of breast cancers have over-expressed HER2 receptor, leading to aggressive behavior of cancer and poor disease course. Implementing anti-HER2 therapy with trastuzumab improved disease outcome and survival of patients. Yet, a significant number of patients do not respond to therapy. HER1, HER2, HER3 and HER4 receptors belong to the epidermal growth factor receptors family. Bonding of growth factor to the receptor activates dimerization of HER receptors, resulting in... More phosphorylation on cytoplasmic domain and activating the signaling pathway. Our study was performed on 124 samples of HER2 positive breast cancer with the assumption that HER2 phosphorylation is a true marker of receptor's activity and that HER2 dimerization with other HER receptors contributes to the acquisition of trastuzumab resistance. We performed immunohistochemical staining using specific primary antibodies against phosphorylated HER2, HER1, HER3 and HER4, and investigated the correlation between their expression and correlation with the resistance. Our results found that HER2 receptor is predominantly phosphorylated (66.2% pHER2+) and positive pHER2 status is a marker of a good response to trastuzumab (P <0.001). Negative phosphorylated status of HER2 is significant in the HER2 intrinsic group where 33.3% of the patients had a disease recurrence. HER1, HER3 and HER4 receptors were expressed in 9.7%, 70.2% and 71% of HER2 positive carcinomas, retrospectively. Coexpression of pHER2 and HER3 showed a statistically significant correlation (P=0.013). Patients with negative pHER2 and positive HER3 or HER4 had poor survival, and resistance was recorded in 35.3% of pHER2‒ /HER3+/HER4+. We can conclude that the positive phosphorylation status of HER2 determines patients who will benefit from trastuzumab therapy. Negative status of pHER2 refers to patients who should undergo dual therapy in first line treatment, especially in the HER2 intrinsic breast cancer group. Less
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:105:704030
Study programmeTitle: Biomedicine and Health Sciences
Study programme type: university
Study level: postgraduate
Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstva (doktor/doktorica znanosti, područje biomedicine i zdravstva)
Type of resourceText
Extent126 str.
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2023-05-05 08:14:06
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