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

Gašljević, Gorana (2016) Određivanje HER2 statusa karcinoma želuca i metastatskih limfnih čvorova upotrebom tkivne mikropostrojbe. PhD thesis, Sveučilište u Zagrebu.

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Abstract

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.

Abstract in Croatian

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.

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