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

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.