Protein IMP3 u solidnim lezijama gušterače

Tadić, Mario (2011) Protein IMP3 u solidnim lezijama gušterače. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Pancreatic ductal adenocarcinoma is a disease with bad prognosis and high mortality. Diagnosis is usually made in late phase of disease that additionally worsen prognosis. Endoscopic ultrasound is capable to evaluate pancreas from close proximity and to acquire tissue sample for cytological diagnosis by EUS guided fine needle aspiration. Sensitivity of detecting malignancy by EUS-FNA is considered high, but in cases with chronic pancreatitis is significantly lower. IMP3 is oncofetal RNA binding protein that is not expressed in benign mature tissue while it is expressed in some cancers. Re-expression of IMP3 in pancreatic ductal adenocarcinoma makes this protein biological marker of malignancy in solid pancreatic lesions. The aim of this study was to assess IMP3 expression in benign pancreatic lesions and pancreatic cancer, to estimate its expression in localized and metastatic pancreatic cancer and to evaluate its role in preoperative diagnostic workup for pancreatic cancer. Lack of IMP3 expression in benign pancreatic lesions, higher level of IMP3 expression in metastatic than in localized pancreatic cancer is hypothesis of this study. We included 75 consecutive patients with solid pancreatic lesions that underwent EUS-FNA for routine diagnostic workout. The patients were divided in three groups, patients with benign lesions, patients with pancreatic cancer localized only on pancreas and patients with metastatic pancreatic cancer. Immunoreactivitiy of IMP3 in benign lesions, localized and metastatic pancreatic cancer was assessed on archived cytological smears sampled by endoscopic ultrasound. IMP3 expression was present in 89% (56/63) of the patients with pancreatic cancer, while none of the patients with benign lesions of pancreas had IMP3 expressed. In 85% of patients with metastatic pancreatic cancer IMP3 was expressed, however, IMP3 protein was expressed in every patient with cancer localized to the pancreas. We found statistically significant positive correlation of stronger expression of IMP3 protein and the stage of the pancreatic cancer. This study proved that expression of IMP3 protein can be assessed on archived cytological smears sampled by endoscopic ultrasound. According to our results, the highest impact would be on differentiation between benign pancreatic lesions and cancer localized to pancreas, however, this should be further investigated, preferably in studies with prospective design.

Abstract in Croatian

Duktalni adenokarcinom gušterače je karcinom sa izrazito lošom prognozom i visokim mortalitetom. Bolest se često dijagnosticira u poodmakloj fazi što dodatno pogoršava prognozu. Endoskopski ultrazvuk je metoda kojom se iz velike blizine može analizirati organ te iz suspektnih lezija uzeti materijal za citološku analizu kako bi se razlučilo radi li se o malignoj ili benignoj leziji. Međutim, iako citološka punkcija pod kontrolom endoskopskog ultrazvuka ima visoku osjetljivost, ona značajno pada u prisutnosti kroničnog pankreatitisa. IMP3 je onkofetalni RNA-vežući protein koji nije izražen u benignom zrelom tkivu dok je prisutan u karcinomima, pa tako i u duktalnom adenokarcinomu gušterače što ga čini interesantnim markerom malignosti kod solidnih lezija gušterače. Cilj ovog istraživanja je utvrditi izraženost IMP3 u benignim lezijama i karcinomima gušterače, utvrditi razliku u izraženosti u lokaliziranom i metastatskom karcinomu te ispitati iskoristivost izraženosti IMP3 u preoperacijskoj dijagnostici karcinoma gušterače. Hipoteza ovog istraživanja je da IMP3 neće biti izražen u benignim lezijama, a da će izraženost biti jača kod metastatskih karcinoma gušterače nego kod lokaliziranih. U ovu studiju uključeno je 75 bolesnika sa solidnim lezijama gušterače koji su podvrgnuti endoskopskom ultrazvuku u sklopu rutinske dijagnostike promjene na gušterači koji s bili podjeljeni u tri skupine, bolesnike s benignim lezijama gušterače, bolesnike s karcinomom lokaliziranim na gušteraču i bolesnike s metastatskim karcinomom. Imunocitokemijski se odredila proteinska izraženost IMP3 u benignim lezijama, karcinomu lokaliziranom na gušteraču i u metastatskom karcinomu gušterače. Procjena izraženosti proteina IMP3 odredila se na nefiksiranim arhiviranim citološkim razmazima dobivenim citološkom punkcijom pod kontrolom endoskopskog ultrazvuka. Izraženost proteina IMP3 imalo je 89% bolesnika (56 od 63) s karcinomom, dok niti jedan bolesnik iz grupe s benignim lezijama gušterače nije imao izraženost proteina IMP3. Protein IMP3 je bio izražen u 85% bolesnika (39 od 46) s metastatskim karcinomom, dok je ekspresija IMP3 bila prisutna u svih bolesnika sa karcinomom lokaliziranim na gušteraču. Našli smo statistički značajnu povezanost između proširenosti duktalnog karcinoma gušterače i jačine izraženosti proteina IMP3. Dokazali smo da se u materijalu dobivenom citološkom punkcijom pod kontrolom EUZ-a može odrediti izraženost proteina IMP3 i na arhivskim staklima. A najveći značaj bi imao u razlikovanju benignih solidnih lezija gušterače i karcinoma lokaliziranih na gušteraču, no to bi svakako trebalo provjeriti u daljnjim studijama.

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