Morphological and functional alterations of the prostate tissue during clinical progression in hormonally‑na&iuml;ve, hormonally‑treated and castration‑resistant patients with metastatic prostate cancer

Korček,Michal; Sekerešová,Monika; Makarevich,Alexander V.; Gavurová,Helena; Olexíková,Lucia; Pivko,Juraj; Barreto,Lenka

doi:10.3892/ol.2020.12064

November-2020 Volume 20 Issue 5

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November-2020 Volume 20 Issue 5

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Morphological and functional alterations of the prostate tissue during clinical progression in hormonally‑naïve, hormonally‑treated and castration‑resistant patients with metastatic prostate cancer

Authors:
- Michal Korček
- Monika Sekerešová
- Alexander V. Makarevich
- Helena Gavurová
- Lucia Olexíková
- Juraj Pivko
- Lenka Barreto
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Affiliations: Department of Urology, Faculty Hospital Nitra, 94901 Nitra, Slovak Republic, Department of Pathology, Faculty Hospital Nitra, 94901 Nitra, Slovak Republic, Research Institute for Animal Production Nitra, National Agricultural and Food Centre, 95141 Lužianky‑near‑Nitra, Slovak Republic

Copyright: © Korček et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Article Number: 201
|
Published online on: September 8, 2020

https://doi.org/10.3892/ol.2020.12064
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Abstract

Since commony used tools in oncological practice for the diagnosis of castration‑resistent prostatic acinar adenocarcinoma are based on clinical criteria, such as castrate testosterone level, continuous rise in serum prostate‑specific antigen, progression of preexisting disease or appearance of new metastases, it is important to identify reliable histopathological markers for the identification of this disease. Therefore, the aim of the present study was to determine the association between results from histological analysis, ultrastructural analysis and apoptosis in the prostate of patients with metastatic acinar prostatic adenocarcinoma (mPC). Patients were treated with androgen deprivation therapy (ADT), abiraterone acetate (Abi) therapy or received no treatment. Prostate tissue samples were divided into four groups as follows: i) Group 1, tissues from patients with benign prostatic hyperplasia (adenocarcinoma negative); ii) group 2, tissues from patients with metastatic hormone naïve prostate cancer; iii) group 3, tissues from patients with mPC treated with ADT; and iv) group 4, tissues from patients with metastatic castration‑resistant prostate cancer treated with ADT and Abi. Immunohistochemical, terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labelling (TUNEL) and ultrastructural assays using light, fluorescence and transmission electron microscopy, respectively, were used to analyze prostate tissue samples. The results demonstrated that ADT and Abi therapy caused histological and ultrastructural changes in prostate tissues. In groups 3 and 4, benign and malignant tissues were affected by the hormonal therapy. Histologically, the malignant epithelium after ADT therapy in groups 3 and 4 presented with a loss of glandular architecture, nuclear and nucleolar shrinkage, chromatin condensation and cytoplasmic clearing. At the ultrastructural level, compact hypertrophic and hyperchromatic nuclei with numerous invaginations were observed in groups 2, 3 and 4. In addition, the incidence of abnormal mitochondria in malignant cells of these groups was high. Group 4 was characterized by the presence of malignant mesenchyme‑like cells in the prostatic stroma, arranged in small groups surrounded by collagen fibrils. Furthermore, the cytoplasm of these cells contained filaments. A decrease in the number of apoptotic cells using TUNEL assays in the examined samples was observed with increasing disease progression. The findings from the present study suggest that the duration of treatment with ADT and progression of the disease were associated with apoptosis dysregulation.

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1	Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI
2	Moch H, Humphrey PA, Ulbright TM and Reuter VI: Tumours of the prostate. WHO Classification of Tumours of the Urinary System and Male Genital Organs. 4th. Humphrey P: IARC; Lyon: pp. 138–162. 2016
3	Cheng L and Bostwick DG: Urologic surgical pathology. E-book. Expert consult title: Online and print. 2nd. Elsevier Health Sciences; pp. 468–513. 2008
4	Epstein JI and Netto GJ: Grading of Prostatic adenocarcinoma. Biopsy interpretation of the prostate. 4th. Pine J and McGough J: Wolters Kluwer and Lippincott Wiliams & Wilkins; pp. 175–198. 2008
5	Bahrami A, Truong LD and Ro JY: Undifferentiated tumor. Arch Pathol Lab Med. 132:326–348. 2008.PubMed/NCBI
6	Lin F and Liu H: Immunohistochemistry in undifferentiated neoplasm/tumor of uncertain origin. Arch Pathol Lab Med. 138:1583–1610. 2014. View Article : Google Scholar : PubMed/NCBI
7	Gleason DF: Histologic grading of prostate cancer: A perspective. Hum Pathol. 23:273–279. 1992. View Article : Google Scholar : PubMed/NCBI
8	Kryvenko ON and Epstein JI: Prostate cancer grading. Arch Pathol Lab Med. 140:1140–1152. 2016. View Article : Google Scholar : PubMed/NCBI
9	Epstein JI, Egewad L, Amin MB, Delahunt B, Srigley JR and Humphrey PA; Grading Committee, : The 2014 International Society of Urological Pathology (ISUP) Consensus conference on Gleason grading of prostatic carcinoma: Definition of grading patterns and proposal for a new grading system. Am J Surg Pathol. 40:244–252. 2016.PubMed/NCBI
10	Khochikar M: Newly proposed prognostic grade group system for prostate cancer: Genesis, utility and its implications in clinical practice. Curr Urol Rep. 17:802016. View Article : Google Scholar : PubMed/NCBI
11	Offermann A, Hohensteiner S, Kuempers C, Ribbat-Idel J, Schneider F, Becker F, Hupe MC, Duensing S, Merseburge AS, Kirfel J, et al: Prognostic value of the new prostate cancer international society of urological pathology grade groups. Front Med (Lausanne). 4:1572017. View Article : Google Scholar : PubMed/NCBI
12	Reuter VE: Pathological changes in benign and malignant prostatic tissue following androgen deprivation therapy. Urology. 49 (Suppl 3A):S16–S22. 1997. View Article : Google Scholar
13	Montironi R and Schulman CC: Pathological changes in prostate lesions after androgen manipulation. J Clin Pathol. 51:5–12. 1998. View Article : Google Scholar : PubMed/NCBI
14	Bostwick DG and Meiers I: Diagnosis of prostatic carcinoma after therapy. Arch Pathol Lab Med. 131:360–371. 2007.PubMed/NCBI
15	Mao P, Nakao K and Angrist A: Human prostatic carcinoma: An electron microscope study. Cancer Res. 26:955–973. 1966.PubMed/NCBI
16	Kaighn ME, Narayan KS, Ohnuki Y, Lechner JF and Jones LW: Establishment and characterization of a human prostatic carcinoma cell line (PC-3). Invest Urol. 17:16–23. 1979.PubMed/NCBI
17	Hernandez-Verdun D: The nucleolus: A model for the organisation of nuclear functions. Histochem. Cell Biol. 126:135–148. 2006.
18	Sun X, Liao NK and Yu JJ: Prognostic value of a mitochondrial functional score in prostate cancer. J Int Med Res. 40:371–376. 2012. View Article : Google Scholar : PubMed/NCBI
19	Kerr JFR, Wyllie AH and Currie AR: Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 26:239–257. 1972. View Article : Google Scholar : PubMed/NCBI
20	Schmied M, Breitschopf H, Gold R, Zichler R, Rothe G, Wekerle H and Lassmannet A: Apoptosis of T lymphocytes in experimental autoimmune encephalomyelitis: Evidence for programmed cell death as a mechanism to control inflammation in the brain. Am J Pathol. 143:446–452. 1993.PubMed/NCBI
21	Elmore S: Apoptosis: A review of programmed cell death. Toxicol Pathol. 35:495–516. 2007. View Article : Google Scholar : PubMed/NCBI
22	Carson DA and Ribeiro JM: Apoptosis and disease. Lancet. 341:1251–1254. 1993. View Article : Google Scholar : PubMed/NCBI
23	Gougeon ML and Montagnier L: Apoptosis in AIDS. Science. 260:1269–1270. 1993. View Article : Google Scholar : PubMed/NCBI
24	Rył A, Rotter I, Kram A, Teresiński L, Słojewski M, Dołęgowska B, Lubkowska A, Piasecka M and Laszczyńska M: Apoptosis and proliferation of the prostate cells in men with benign prostatic hyperplasia and concomitant metabolic disorders. Histol Histopathol. 33:389–397. 2017.PubMed/NCBI
25	Gaffney EF: The extent of apoptosis in different types of high-grade prostatic carcinoma. Histopathology. 25:269–273. 1994. View Article : Google Scholar : PubMed/NCBI
26	Aihara M, Truong LD, Dunn JK, Wheeler TM, Scardino PT and Thompson TC: Frequency of apoptosis bodies positively correlates with Gleason grade in prostate cancer. Hum Pathol. 25:797–801. 1994. View Article : Google Scholar : PubMed/NCBI
27	Aihara M, Scardino PT, Truong LD, Wheeler TM, Goad JR, Yang G and Thompson TC: The frequency of apoptosis correlates with the prognosis of Gleason grade 3 adenocarcinoma of the prostate. Cancer. 75:522–529. 1995. View Article : Google Scholar : PubMed/NCBI
28	Staunton MJ and Gaffney EF: Tumor type is a determinant of susceptibility to apoptosis. Am J Clin Pathol. 103:300–307. 1995. View Article : Google Scholar : PubMed/NCBI
29	Drachenberg CB, Ioffe OB and Papadimitriou JC: Progressive increase of apoptosis in prostatic intraepithelial neoplasia and carcinoma: Comparison between in situ end-labeling of fragmented DNA and detection by routine hematoxylin-eosin staining. Arch Pathol Lab Med. 121:54–58. 1997.PubMed/NCBI
30	Edge SB and Compton CC: The American Joint Committee on Cancer: The 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 17:1471–1474. 2010. View Article : Google Scholar : PubMed/NCBI
31	Mottet N, Bellmunt J, Bolla M, Briers E, Cumberbatch MG, De Santis M, Fossati N, Gross T, Henry AM, Joniau S, et al: EAU-ESTRO-SIOG Guidelines on prostate cancer. Part 1: Screening, diagnosis, and local treatment with curative intent. Eur Urol. 71:618–629. 2017. View Article : Google Scholar : PubMed/NCBI
32	Reynolds ES: The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J Cell Biol. 17:2081963. View Article : Google Scholar : PubMed/NCBI
33	Têtu B: Morphological changes induced by androgen blockade in normal prostate and prostatic carcinoma. Best Pract Res Clin Endocrinol Metab. 22:271–283. 2008. View Article : Google Scholar : PubMed/NCBI
34	Krakhmal NV, Zavyalova MV, Denisov EV, Vtorushin SV and Perelmuter VM: Cancer invasion: Patterns and mechanisms. Acta Naturae. 7:17–28. 2015. View Article : Google Scholar : PubMed/NCBI
35	Sebastiano C, Vincenzo F, Tommaso C, Giuseppe S, Marco R, Ivana C, Giorgio R, Massimo M and Giuseppe M: Dietary patterns and prostatic diseases. Front Biosci (Elite Ed). 4:195–204. 2012. View Article : Google Scholar : PubMed/NCBI
36	Stoff JA: Selected office based anticancer treatment strategies. J Oncol. 2019:74625132019. View Article : Google Scholar : PubMed/NCBI
37	Hickmen JA: Apoptosis induced by anti-cancer drugs. Cancer Metastasis Rev. 11:121–139. 1992. View Article : Google Scholar : PubMed/NCBI
38	D'Arcy MS: Cell death: A review of the major forms of apoptosis, necrosis and autophagy. Cell Biol Int. 43:582–592. 2019. View Article : Google Scholar : PubMed/NCBI
39	Li M, Yang X, Wang H, Xu E and Xi Z: Inhibition of androgen induces autophagy in benign prostate epithelial cells. Int J Urol. 21:195–199. 2014. View Article : Google Scholar : PubMed/NCBI
40	Krajewska M, Krajewski S, Epstein JI, Shabaik A, Sauvageot J, Song K, Kitada S and Reed JC: Immunohistochemical analysis of bcl-2, bax, bcl-X, and mcl-1 expression in prostate cancers. Am J Pathol. 148:1567–1576. 1996.PubMed/NCBI
41	Srivastava SK, Bhardwaj A, Singh S, Arora S, McClellan S, Grizzle WE, Reed E and Singh AP: Myb overexpression overrides androgen depletion-induced cell cycle arrest and apoptosis in prostate cancer cells, and confers aggressive malignant traits: Potential role in castration resistance. Carcinogenesis. 33:1149–1157. 2012. View Article : Google Scholar : PubMed/NCBI
42	Sun BO, Fang Y, Li Z, Chen Z and Xiang J: Role of cellular cytoskeleton in epithelial-mesenchymal transition process during cancer progression. Biomed Rep. 3:603–610. 2015. View Article : Google Scholar : PubMed/NCBI
43	Shankar J, Messenberg A, Chan J, Underhill TM, Foster LJ and Nabi IR: Pseudopodial actin dynamics control epithelial-mesenchymal transition in metastatic cancer cells. Cancer Res. 70:3780–3790. 2010. View Article : Google Scholar : PubMed/NCBI
44	Jolly MK and Celià-Terrassa T: Dynamics of phenotypic heterogeneity associated with emt and stemness during cancer progression. J Clin Med. 8:15422019. View Article : Google Scholar