Određivanje HER2 statusa karcinoma želuca i metastatskih limfnih čvorova upotrebom tkivne mikropostrojbe

doctoral thesis

• Author: Gorana Gašljević
• Mentor: Slavko Gašparov (mentor)
• Committee member: nije dostupno (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2016-06-29, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences
• Universal decimal classification (UDC): 61 - Medical sciences

Abstract

Karcinom želuca je jedna od najčešćih malignih bolesti u ljudi s gotovo milijun
novodijagnosticiranih slučajeva u svijetu godišnje i petogodišnjim preživljenjem od
svega 20%. Još uvijek ne postoje standardizirani i opće prihvaćeni kemoterapijski
protokoli za njegovo liječenje, a budući se bolest najčešće dijagnosticira u vrlo
uznapredovalom stadiju, u najvećem broju slučajeva kemoterapija ima samo
palijativnu namjenu. Zbog toga je potrebno pronaći i uvesti nove terapijske
mogućnosti koje bi dovele do produženja preživljenja pacijenata s lokalno
uznapredovalim ili metastatskim karcinomom želuca. Budući da je oko 15%
karcinoma želuca pozitivno za HER2, upravo se ta molekula koja se nalazi na
površini stanice ponudila kao eventualna ciljna molekula koju bi se moglo blokirati
već postojećim antiHER2 monoklonskim protutijelima. 2010. godine su objavljeni
rezultati prve velike, internacionalne randomizirane studije u kojoj je postignuta
tumorska regresija, produljenje preživljenja i produljenje vremena do relapsa u
skupini pacijenata s HER2 pozitivnim karcinomom želuca koji su bili tretirani
kombinacijom kemoterapeutika i monoklonskog protutijela za HER2, u odnosu na
one koji su dobivali samo kemoterapiju. Testiranje HER2 na karcinomu želuca ulazi u
rutinu, a 2012. godine stvorene su smjernice koje diktiraju način rukovanja
materijalom te očitavanje rezultata. Vrlo brzo postaje jasno da primjena tih smjernica
dovodi do toga da se dio karcinoma koji su HER2 pozitivni ne prepozna i da se takve
pacijente ne liječi adekvatno. Načelno je mišljenje da testiranje HER2 na jednom
bloku tumorskog tkiva nije dovoljno kao i da ocjena HER2 statusa na bioptičnom
materijalu nije adekvatni ekvivalent testiranja na cijelom tkivnom bloku. Rezultati
naše studije pokazuju da bi se problem heterogenosti za HER2 u karcinomu želuca
mogao premostiti upotrebom tehnologije tkivnih mikropostrojbi koje bi omogućile
testiranje veće količine tumorskog tkiva u kratkom vremenskom roku i s bitno manjim
troškovima testiranja nego što bi bili s testiranjem većeg broja standardnih rezova.

Abstract (english)

Stomach cancer is one of the most common malignant diseases in human
population. There are almost one million of newly diagnosed cases each year.
Five year survival is only about 20%. There are still no standardized or generally
accepted chemotherapy protocols for its treatment. Since the disease is usually
diagnosed at a very advanced stage, treatment is only palliative. Therefore, it is
necessary to find and to introduce new therapeutic options which could extend
the survival of patients with locally advanced or metastatic gastric cancer. About
15% of stomach carcinomas are positive for HER2. HER2 is a molecule which
was found at the cell surface of the different human malignancies including gastric
cancer. It represents target molecule that can be blocked by use of monoclonal
antiHER2 antibodies. In 2010 the results of the first, international and randomized
study about antiHER2 therapy of metastatic gastric carcinoma were published.
The study showed regression of the primary tumor, prolongation of survival and
prolongation of the relapsing time in the group of patient that had been treated
with combination of chemotherapy and antiHER2 antibody in comparison with
patients that had been treated with chemotherapy only. The very same year
HER2 testing for gastric cancer was introduced into routine. In 2012. first
guidelines about proper testing protocol were published. Very soon it became
clear that the application of guidelines, in the meaning of HER2 testing at the one
section of the resected tumor or at the endoscopic material, results in too many
false negative tumors. There is an opinion that endoscopic material cannot be
used as an equivalent for HER2 testing at the whole section. Also, testing at the
one tumor block is not necessarily enough because of known HER2 heterogeneity
of gastric cancer. The results of our study show that the problem of HER2
heterogeneity of gastric cancer could be »bypassed« by the use of tissue
microarrays. Technology of tissue microarrays would enable the testing of larger
volume of tumor tissue within short period of time and in significantly lower cost in
comparison with testing at the whole sections of the tumor tissue.

• Keywords: medicina
• Keywords (english): medicine
• Language: croatian
• URN:NBN: urn:nbn:hr:105:672915
• Study programme: Title: 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 resource: Text
• Extent: 83 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-05-05 08:00:42