Ekspresija estrogenog receptora β u prekanceroznim lezijama i adenokarcinomu prostate

Abstract

Adenokarcinom prostate (PCa) je najčešći karcinom u muškaraca. Intraepitelne prostatične neoplazme visokog gradusa (HGPIN) su lezije koje prethode nastanku invazivnog karcinoma i podrazumevaju kompletno odsustvo bazalnih ćelija i invaziju strome malignim acinusima. Estrogeni receptor β (ERβ) se nalazi u jedrima bazalnih i sekretornih ćelija acinusa i delimično u stromalnim ćelijama. Cilj istraživanja je da prikaže i lokalizuje ERβ u različitim morfološkim lezijama prostate: hiperplaziji (BHP), PINu i u PCa sa različitim Gleason scorom. Pretpostavlja se da prekancerozne lezije u svojim različitim fazama evolucije ne koreliraju u potpunosti sa ekspresijom ERβ. LGPIN pokazuje ekspresiju, dok u HGPINu nema ekspresije. Takođe je pretpostavka da ekspresija ERβ postoji u većine srednje diferentovanih PCa, te da se ekspresija posmatranog receptora gubi sa porastom Gleason scora. Ispitivano je pet grupa bolesnika: kontrolna grupa sa BHP i četiri eksperimentalne grupe (PIN i 3 različite grupe PCa). Studija je sprovedena na muškarcima različite starosti u periodu 2010–2012. Nijedan pacijent nije prethodno primio hormonsku terapiju. Sekstant biopsije prostate su bojene na ERβ (Novocastra). Lokalizacija i intenzitet ERβ ekspresije prikazani su kroz skor: 0 = nula; 1 = <1%; 2 = 1–10%; 3 = 11–33%; 4 = 34–66%; 5 = > 66%. Pozitivni fibroblasti i endotelne ćelije su korišćene za poređenje. Smanjena ekspresija ERβ primećena je kod malignih i premalignih lezija prostate naspram BHP. Ekspresija ERβ u epitelnim ćelijama acinusa bila je najslabija u dobro diferentovanim PCa. Kod BHP i dobro diferentovanih PCa bila je veća ekspresija ERβ u bazalnim ćelijama nego u sekretornim. Loše diferentovani PCa prikazali su smanjenje ekspresije ERβ u bazalnim ćelijama. Ukupna ćelijska ekspresija ERβ predstavlja složen i ponekad moguće paradoksalan nalaz, na osnovu čega primarni PCa zadržava ekspresiju ovog receptora, ali ipak značajno nižu u poređenju sa benignim epitelom i premalignim lezijama. Ovaj nalaz podupire stanovište o antiproliferativnoj ulozi ERβ u tkivu prostate.

Adenocarcinoma of the prostate (PCa) is the most common cancer in men. High-grade prostatic intraepithelial neoplasia (HGPIN) are lesions that precede to invasive carcinomas and include complete absence of basal cells and stromal invasion by malignant acini. Estrogen receptor ß(ERß) is located in the nuclei of basal and secretory cells and partly in stromal ones.The aim of the research is to describe and localize ERß in different morphological lesions: prostate hyperplasia (BPH), PIN and PCa with different Gleason score. It is assumed that pre-cancerous lesions in different stages of their evolution not correlate completely with the expression ERß. LGPIN shows expression, while there is no expression in HGPIN. It is also an assumption that the expression ERß exists in most medium differentiated PCa, and that the expression of this receptor loses with increasing of Gleason score. Five groups of patient were investigated: control group with BPH and four experimental groups (PIN and 3 different groups of PCa). The study was conducted on men of different ages in the period 2010-2012. None of the patients received prior hormonal therapy. Sextant prostate biopsy were stained on ERß (Novocastra). ERß expression is shown through the score: 0 = zero; 1 = <1%; 2 = 1-10%; 3 = 11-33%; 4 = 34-66%; 5 => 66%. Positive fibroblasts and endothelial cells were used for comparison. Reduced expression was observed in malignant and premalignant lesions of the prostate versus BPH. ERß expression in the epithelial cells of acini was the weakest in well-differentiated PCa. In BPH and well differentiated PCa was greater expression in the basal cells than in secretory ones. Poorly differentiated PCa showed a decreased ERß expression in basal cells. Total cellular expression of ERß is a complex and sometimes paradoxical finding on the basis of which the primary PCa retains expression of this receptor, but significantly lower compared to benign epithelium and premalignant lesions. This finding supports the antiproliferative role of ERß in prostate tissue.