The expression and localization of estrogen receptor beta in hyperplastic and neoplastic prostate lesions

Aleksandra Fejsa Levakov; Mihaela Mocko Kaćanski; Nada Vučković; Mirjana Živojinov; Jelena Amidžić; Jelena Ilić Sabo

doi:10.2298/4717

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

Keywords: prostatic neoplasms, adenocarcinoma, estrogen receptor beta,

Abstract

Background/Aim. Benign acini in benign prostatic hyperplasia (BPH) are lined with pseudostratified cylindrical epithelium with a continuous basal cell layer. Adenocarcinoma of the prostate is the most common cancer in men. High gradus-prostatic intraepithelial neoplasia (HGPIN) lesions precede invasive cancer. Prostate adenocarcinoma (PCa) implies a complete absence of basal cells and stromal invasion by malignant acini. Estrogen receptor (ER) is located in nuclei of acinar basal and secretory cells and partially in stromal cells. The aim of this research was to demonstrate and localize ER in BPH and in PCa of different Gleason scores. Considering literature data for ER-beta expression in different morphologic prostate lesions, it is assumed that there is expression of ER-beta in most moderately differentiated PCa, and that the observed receptor expression is lost with increasing of the Gleason score. Methods. Four groups of patients were formed: the control with BPH and three experimental groups with PCa of different grades and scores, according to the Gleason grading system. The patients were male of various ages suspected of PCa, based on clinical and laboratory parameters. The study was conducted in a period 2010–2012. None of the patients received prior hormonal therapy. Sextant byopsies with BPH and PCa were treated for ER-beta (Novocastra). Localization and intensity of ER-beta expression is reported through the score: 0 = zero; 1 = < 1%; 2 = 1–10%; 3 = 11–33%; 4 = 34–66%; 5 – > 66%. Positive fibroblasts and endothelial cells are used for comparison. Results. ER-beta expression in acinar epithelial cells was the weakest in well-differentiated adenocarcinoma. A decline of ER-beta expression was noticed in malignant lesions of the prostate vs benign ones. Less differentiated adenocarcinomas showed a decrease of ER-beta expression in basal and in the secretory cells. ER-beta expression in basal cells was stronger than in secretory ones in BPH and well-differentiated adenocarcinoma. Conclusion. ER-beta expression was most pronounced in BHP samples and declined in malignant prostatic lesions. This finding supports statement on antiproliferative role of ER-beta in prostatic tissue.

Author Biography

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

References

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.