Prognostička vrijednost određivanja nm23, MAGE-3 i NY-ESO-1 u planocelularnim karcinomima glave i vrata

Pastorčić-Grgić, Marija (2010) Prognostička vrijednost određivanja nm23, MAGE-3 i NY-ESO-1 u planocelularnim karcinomima glave i vrata. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Head and neck squamous cell cancer is a group of tumors characterised by unique histological findings, the same etiological factors and frequent appereance of several cancers in the same patient. Metastasing is the most importrant accepted prognostic factor. Nm23 gene is one of the genes that suppress metastatic potential. Low expression of nm23 is associated with poor prognosis and more frequent metastasis in several types of cancers. MAGE-3 and NY-ESO-1 genes encoding antigenes expressed in a number of tumours with different hystology. Antigenes are recognized by CD8 (+) T lymphocytes. Antigen NY-ESO- 1 is considered one of the most immunogenic antigens. Retrospective research included 198 patients treated for head and neck squamous cell cancer. Immunohistochemical analysis of nm23, MAGE-3 and NY-ESO-1 expression was performed. We investigated the correlation between nm23, MAGE-A and NY-ESO-1 expression and tumor localization, TNM stage, histological grade and disease specific survival. Gene nm23 was expressed in 56.6% of tumors. The proportion of nm23 positive tumors in the group of patients with oral cavity and laryngeal cancer was lower (46.3%) than in the group of patients with the oropharyngeal and hypopharyngeal cancer (68.8%). The expression of nm23 gene in all patients showed no correlation with TNM stage, histological grade, nor the 5-year survival rate. The analysis of expression of only one gene, which is a part of a complex metastatic process, is not sufficient to differentiate tumors with high and low metastatic potential. MAGE-3 gene was expressed in 66.7% of analyzed sample showed no correlation of expression with localization, TNM stage, histological grade, nor survival. Although it is not a good prognostic factor, it could be a good target for immunotherapy. A large proportion of MAGE-3 positive tumors implicates the need to examine the effectiveness of immunotherapy in squamous cell head and neck cancer. The expression of NY-ESO-1 gene was present in 34.4% of analyzed tumors, and it was less frequently present in poorly differentiated carcinomas. It was a predictor of better prognosis. Due to a small proportion of tumors that show the expression of NY-ESO-1, the potential of clinical implementation is small.

Abstract in Croatian

Planocelularni karcinomi glave i vrata su skupina tumora koju karakterizira jedinstvena patohistološka slika, isti etiološki čimbenici i često pojavljivanje nekoliko tumora kod istog bolesnika. Metastaziranje tumora najvažniji je prihvaćeni prognostički čimbenik. Gen nm23 jedan je od gena koji suprimiraju metastatski potencijal tumora. Niska izraženost proteina nm23 povezana je s lošom prognozom i učestalijim metastazama u nekoliko vrsta karcinoma. Geni MAGE-3 i NY-ESO-1 kodiraju antigene izražene u velikom broju tumora različite histologije. Antigene prepoznaju CD8 (+) T limfociti. Antigenski produkt gena NYESO- 1 smatra se jednim od najimunogenijih izoliranih antigena. Provedeno je retrospektivno istraživanje u koje je uključeno 198 bolesnika s planocelularnim karcinomom glave i vrata. Učinjena je imunohistokemijska obrada izraženosti nm23, MAGE-3 i NY-ESO-1. Analizirana je povezanost izraženosti proteina nm23, MAGE-3 i NY-ESO-1 s lokalizacijom, proširenosti tumora (TNM) u trenutku postavljanja dijagnoze, s histološkim stupnjem diferenciranosti tumora, te s preživljenjem bolesnika. Nm23 izražen je u ukupno 56.6% tumora. Udio nm23 pozitivnih tumora u skupini bolesnika s karcinomom usne šupljine i larinksa bio je manji (46.3%) nego u skupini bolesnika s karcinomom orofarinksa i hipofarinksa (68.9%). Izraženost proteina nm23 u svim uključenim planocelularnim karcinomima glave i vrata nije pokazala povezanost s TNM stadijem, histološkim stupnjem diferenciranosti tumora, kao ni 5-godišnjim preživljenjem. Analiza izraženosti samo jednog od proteina koji je dio složenog metastatskog procesa nedovoljna je za razlikovanje tumora s niskim i visokim metastatskim potencijalom. MAGE-3 izražen je u 66.7% analiziranih uzoraka. Na analiziranom uzorku nije pokazana povezanost izraženosti s lokalizacijom, TNM stadijem, histološkim stupnjem diferenciranosti, kao ni preživljenjem. Iako nije dobar prognostički čimbenik, mogao bi biti dobar cilj imunoterapije. Veliki udio MAGE-3 pozitivnih tumora ukazuje na potrebu istraživanja učinkovitosti imunoterapije u planocelularnim karcinomima glave i vrata. Izraženost NY-ESO-1 postojala je u 34.3% analiziranih tumora, a pojavljivala se rjeĎe kod histološki slabije diferenciranih karcinoma, te je bila prediktor bolje prognoze. Zbog malog udjela tumora koji pokazuju izraženost NY-ESO-1 vjerojatnost kliničke primjene je mala.

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