Ekspresija i lokalizacija estrogenog receptora beta kod hiperplastičnih i neoplastičnih lezija prostate

  • Aleksandra Fejsa Levakov Pathology and Histology Center, Clinical Center of Vojvodina, Novi Sad, Serbia; Department for Histology and Embryology Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
  • Mihaela Mocko Kaćanski Pathology and Histology Center, Clinical Center of Vojvodina, Novi Sad, Serbia; Department for Histology and Embryology Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
  • Nada Vučković Pathology and Histology Center, Clinical Center of Vojvodina, Novi Sad, Serbia Department for Pathology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
  • Mirjana Živojinov Pathology and Histology Center, Clinical Center of Vojvodina, Novi Sad, Serbia Department for Pathology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
  • Jelena Amidžić Pathology and Histology Center, Clinical Center of Vojvodina, Novi Sad, Serbia; Department for Histology and Embryology Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
  • Jelena Ilić Sabo Pathology and Histology Center, Clinical Center of Vojvodina, Novi Sad, Serbia; Department for Histology and Embryology Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
DOI: https://doi.org/10.2298/4717
Ključne reči: prostatic neoplasms||, ||prostata, neoplazme, adenocarcinoma||, ||adenokarcinom, estrogen receptor beta||, ||receptor, estrogenski, beta,

Sažetak


Uvod/Cilj. Benigni acinusi kod benigne hiperplazije prostate (BHP) obloženi su pseudostratifikovanim cilindričnim epitelom sa kontinuiranim slojem bazalnih ćelija. Adenokarcinom prostate najčešći je karcinom kod muškaraca. Intraepitelne prostatične neoplazme visokog gradusa (HGPIN) su lezije koje prethode nastanku invazivnog karcinoma (Pca) i podrazumevaju kompletno odsustvo bazalnih ćelija i invaziju strome malignim acinusima. Estrogeni receptor (ER) beta nalazi se u jedrima bazalnih i sekretornih ćelija acinusa i delimično u stromalnim ćelijama. Cilj ovog istraživanja bio je da se prikaže i lokalizuje ER beta u BHP, kao i u PCa sa različitim Gleason skorom. S obzirom na podatke iz literature o ekspresiji ER beta u različitim morfološkim lezijama prostate, pretpostavlja se da je ekspresija ER beta prisutna u većini srednje diferentovanih PCa, i da se ekspresija posmatranog receptora gubi sa povećanjem Gleason scora. Metode. Ispitivane su četiri grupe bolesnika: kontrolna grupa sa BHP i tri eksperimentalne grupe sa PCa različitih gradusa i skorova prema Gleason-ovom sistemu. Bolesnici su bili muškarci različite starosti sa sumnjom na PCa, na osnovu kliničkih i laboratorijskih parametara. Studija je sprovedena u periodu 2010–2012. Nijedan od bolesnika nije prethodno primio hormonsku terapiju. Sekstant biopsije sa nalazom BHP i PCa bojene su na ER beta (Novocastra). Lokalizacija i intenzitet ER beta 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 korišćene su za poređenje. Rezultati. Ekspresija ER beta u epitelnim ćelijama acinusa bila je najslabija u dobro diferentovanim adenokarcinomima. Smanjena ekspresije ER beta primećena je kod malignih lezija prostate naspram benignih lezija. Loše diferentovani adenokarcinomi prikazali su smanjenje ekspresije ER beta u bazalnim i sekretornim ćelijama. Kod BHP i dobro diferentovanih adeniokarcinomima bila je veća ekspresija ER beta u bazalnim ćelijama nego u sekretornim. Zaključak. Ekspresija Er-beta receptora B najizraženija je u uzorcima tkiva prostate bolesnika sa BHP i smanjuje se kod adenokarcinoma prostate. Ovaj nalaz podupire stanovište o antiproliferativnoj ulozi ER-beta u tkivu prostate.

Biografija autora

Aleksandra Fejsa Levakov, Pathology and Histology Center, Clinical Center of Vojvodina, Novi Sad, Serbia; Department for Histology and Embryology Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
Center for pathology and histology

Reference

Rosai J. Rosai and Ackerman's surgical pathology. 9th ed. Phila-delphia: Mosby, Elsevier Inc; 2004.

Gabal SM, Habib FM, Helmy DO, Ibrahim MF. Expression of estrogen receptor-B (ER-B) in bengin and malignant prostatic epithelial cells and its correlation with the clinico-pathological features. J Egypt Natl Canc Inst 2007; 19(4): 239−48.

De Marzo AM, Platz EA, Sutcliffe S, Xu J, Grönberg H, Drake CG, et al. Inflammation in prostate carcinogenesis. Nat Rev Cancer 2007; 7(4): 256−69.

de Marzo AM, Nelson WG, Isaacs WB, Epstein JI. Pathological and molecular aspects of prostate cancer. Lancet 2003; 361(9361): 955−64.

Bostwick DG, Qian J. High-grade prostatic intraepithelial neo-plasia. Mod Pathol 2004; 17(3): 360−79.

Montironi R, Mazzucchelli R, Lopez-Beltran A, Cheng L, Scarpelli M. Mechanisms of Disease: high-grade prostatic intraepithelial neoplasia and other proposed preneoplastic lesions in the prostate. Nature Clin Pract Urol 2007; 4(6): 321−32.

McPherson SJ, Ellem SJ, Simpson ER, Patchev V, Fritzemeier K, Ris-bridger GP. Essential role for estrogen receptor beta in stromal-epithelial regulation of prostatic hyperplasia. Endocrinology 2007; 148(2): 566−74.

Risbridger GP, Ellem SJ, McPherson SJ. Estrogen action on the prostate gland: a critical mix of endocrine and paracrine signal-ing. J Mol Endocrinol 2007; 39(3): 183−8.

Leav I, Lau KM, Adams JY, McNeal JE, Taplin ME, Wang J, et al.. Comparative studies of the estrogen receptors beta and alpha and the androgen receptor in normal human prostate glands, dysplasia, and in primary and metastatic carcinoma. Am J Pathol 2001; 159(1): 79−92.

Prins GS, Korach KS. The role of estrogens and estrogen recep-tors in normal prostate growth and disease. Steroids 2008; 73(3): 233−44.

Pasquali D, Rossi V, Esposito D, Abbondanza C, Puca GA, Bellastella A, et al. Loss of estrogen receptor beta expression in malignant human prostate cells in primary cultures and in prostate cancer tissues. J Clin Endocrinol Metab 2001; 86(5): 2051−5.

Weihua Z, Warner M, Gustafsson J. Estrogen receptor beta in the prostate. Mol Cell Endocrinol 2002; 193(1−2): 1−5.

Fixemer T, Remberger K, Bonkhoff H. Differential expression of the estrogen receptor beta (ERbeta) in human prostate tissue, premalignant changes, and in primary, metastatic, and recur-rent prostatic adenocarcinoma. Prostate 2003; 54(2): 79−87.

Horvath LG, Henshall SM, Lee CS, Head DR, Quinn DI, Makela S, et al. Frequent loss of estrogen receptor-beta expression in prostate cancer. Cancer Res 2001; 61(14): 5331−5.

Stettner M, Kaulfuss S, Burfeind P, Schweyer S, Strauss A, Ringert R, et al. The relevance of estrogen receptor-beta expression to the antiproliferative effects observed with histone deacetylase inhibitors and phytoestrogens in prostate cancer treatment. Mol Cancer Ther 2007; 6(10): 2626−33.

Steiner MS, Raghow S. Antiestrogens and selective estrogen re-ceptor modulators reduce prostate cancer risk. World J Urol 2003; 21(1): 31−6.

Cheng J, Lee EJ, Madison LD, Lazennec G. Expression of estro-gen receptor beta in prostate carcinoma cells inhibits invasion and proliferation and triggers apoptosis. FEBS Lett 2004; 566(1−3): 169−72.

Kuiper GG, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson JA. Cloning of a novel receptor expressed in rat prostate and ova-ry. Proc Natl Acad Sci U S A 1996; 93(12): 5925−30.

Royuela M, de Miguel MP, Bethencourt FR, Sánchez-Chapado M, Fraile B, Arenas MI, et al. Estrogen receptors alpha and beta in the normal, hyperplastic and carcinomatous human prostate. J Endocrinol 2001; 168(3): 447−54.

Bonkhoff H, Fixemer T, Hunsicker I, Remberger K. Estrogen recep-tor expression in prostate cancer and premalignant prostatic lesions. Am J Pathol 1999; 155(2): 641−7.

Signoretti S, Loda M. Estrogen receptor beta in prostate cancer: brake pedal or accelerator. Am J Pathol 2001; 159(1): 13−6.

Hartman J, Ström A, Gustafsson JÅ. Current concepts and signif-icance of estrogen receptor β in prostate cancer. Steroids 2012; 77(12): 1262−6.

Asgari M, Morakabati A. Estrogen receptor beta expression in prostateadenocarcinoma. Diagn Pathol 2011; 6: 61.

McPherson SJ, Hussain S, Balanathan P, Hedwards SL, Niranjan B, Grant M, Risbridger GP. Estrogen receptor-beta activated apoptosis in benign hyperplasia and cancer of the prostate is androgen independent and TNFalpha mediated. PNAS 2010; 107(7): 3123−8.

Vojinov S, Levakov I, Jeremić D, Zivojinov S, Marusić G. Hormonal status in patients with advanced prostatic cancer on the thera-py with androgen blockade. Vojnosanit Pregl 2011; 68(4): 321−6.

Objavljeno
2015/11/02
Broj časopisa
Vol. 72 Br. 10 (2015)
Rubrika
Originalni članak