Imunohistohemijsko proučavanje neovaskularizacije i proliferativne aktivnosti tumora paratiroidne žlezde

Abstract

Teško je razlikovati paratireoidne karcinome (PC) od paratireoidnih adenoma samo na osnovu histopatoloških 100 karakteristika. Na osnovu postojeće literature, ova doktorska disertacija je prva koja istražuje ekspresiju CD105 (endoglina) u angiogenim endotelnim ćelijama PC. CD 105 antitela su pogodna u određivanju mikrovaskularne gustine (MVD). Ki67 se koristi kao marker ćelijske proliferacije. Određivanje ekspresije markera ćelijske proliferacije (Ki67) i neoangiogeneze (CD 105) i njihove povezanosti sa serumskim nivoima PTH i klasičnim prognostičkim parametrima paratiroidnih adenoma i karcinoma. MATERIJAL I METODE: Retrospektivna analiza sprovedena je na 50 bolesnika kod kojih je patohistološki potvrđen primarni hiperparatiroidizam: 10 pacijenata obolelih od karcinoma paratiroidne žlezde i 40 od adenoma. Normalne paratiroidne žlezde su korišćene kao kontrolna grupa. U standardnoj imunohistohemijskoj proceduri, monoklonska antitela endoglina su primenjena za detekciju angiogenih endotelnih ćelija. Imunološko bojenje je procenjeno analizom slike i statistička analiza je kasnije izvršena. REZULTATI: Zaključeno je da Ki67 bio viši u PC pacijenata (medijana = 523,43) u poređenju sa pacijentima obolelim od adenoma (medijana = 297,41). Mann–Whitney U testom dobijena je visoko statistički značajna razlika između ove dve grupe (U = 10.50; Z = 4.598; p < 0.001). MVD bila je veća u PC pacijenata (medijana = 901,14) u odnosu na pacijenate obolele od adenoma (medijana = 431.24). Mann–Whitney U testom dobijena je takođe visoko statistički značajna razlika između grupa (U = 41,50; Z = 3,845; p < 0,001). U ovoj studiji, ekspresija endoglin nije pronađena u krvnim sudovima normalnih 101 paratireoidnih žlezda. Iz ROC krive se može videti da oba markera imaju dobru prediktivnu vrednost za dijagnozu karcinoma. Pokazana je i njihova korelacija sa ostalim obeležjima. Zaključili smo da je serumski nivo preoperativnog PTH koristan za predikciju paratiroidnih karcinoma i da on visoko statistički značajno koreliše još sa težinom tumora, sa promerom tumora, sa vrednostima Ca preoperativno i sa Ki-67 i MVD. Veličina paratiroidnih tumora može biti važan faktor u predviđanju paratiroidnih karcinoma kod pacijenata sa primarnim hiperparatiroidizmom. Takođe, smo utvrdili da je veća verovatnoća da bolesnik sa velikom težinom tumora ima karcinom nego adenom. ZAKLjUČAK: Primećeno je u studiji da postoji veća stopa angiogeneze i ćelijske proliferacije u malignim tumorima u odnosu na benigne, što ukazuje na ulogu ovih tumora u malignitetu i agresivnijem ponašanju. Štaviše, ekspresioni profili biomarkera Ki67 i CD105 u ovoj studiji predstavljaju potencijalne markere maligniteta ili ciljeve nove terapije u bolesnika sa karcinomom paratiroidne žlezde (PC).

INTRODUCTION: It is difficult to distinguish parathyroid carcinoma (PC) from parathyroid adenoma on the basis of histopathological features alone. As far as is known to the authors based on the existing literature, the present study 105 is the first to investigate CD105 (Endoglin) expressed in angiogenic endothelial cells of PC. CD 105 antibodies are suitable in determining microvessel density (MVD). Ki67 is used as a marker for cell proliferation. AIM: To determine expression of two markers of cell proliferation (Ki67) and their angiogenesis (CD 105 ) and as well as correlation with serum PTH levels and classic prognostic parameters of parathyroid adenoma and carcinoma. MATERIALS AND METHODS: A retrospective analysis of 50 patients who have pathologically confirmed primary hyperparathyroidism (PHPT) was conducted: 10 patients suffering from PC and 40 patients suffering from adenoma. Normal parathyroid glands served as the control group. In a standard immunohistochemical procedure, monoclonal antibodies to Endoglin, were applied to detect angiogenic endothelial cells. Immunostaining was estimated through image analysis and a statistical analysis was subsequently performed. RESULTS: It was concluded that Ki67 was higher in PC patients (median= 523.43) compared to adenoma patients (median = 297.41). A Mann–Whitney U-test shows the difference to be significant between the two groups (U = 10.50; Z = 4.598; p < 0.001). MVD was higher in PC patients (median= 901.14) than in adenoma patients (median = 431.24). A Mann–Whitney U-test also has shown the difference to be significant (U = 41.50; Z = 3.845; p<0.001). In this study, the expression of Endoglin was not found in the blood vessels of normal parathyroid glands. The ROC curve also demonstrates that both markers have a beneficial predictive value in the diagnosis of cancer. Their correlation with other factors was also found. It was concluded that preoperative serum levels ofcarcinoma, as PTH is highly statistically significantly since in correlates with the weight of the tumour, with the diameter of the tumour, with the values of Ca preoperative and Ki67, as well as MVD. Parathyroid tumour size can be an important factor in predicting parathyroid carcinoma in patients with primary hyperparathyroidism. In addition, it was found that a patient with a greater tumour weight will also have a higher probability of cancer than of adenoma. CONCLUSION: The study has observed that there is a higher rate of angiogenesis and cellular proliferation in malignant tumours compared to benign tumours, indicating their role in the malignancy and aggressive behaviour of these tumours. Moreover, the expression profile of the biomarkers Ki67 and CD105 in this study represents potential markers of malignancy or targets for novel therapies in patients with parathyroid carcinoma (PC).