Apoptotic and predictive factors by Bax, Caspases 3/9, Bcl-2, p53 and Ki-67 in prostate cancer after 12 Gy single-dose

• Published in: Scientific reports 2020-04, Vol.10 (1), p.7050-7050, Article 7050
• Main Authors: Pisani, Carla, Ramella, Martina, Boldorini, Renzo, Loi, Gianfranco, Billia, Michele, Boccafoschi, Francesca, Volpe, Alessandro, Krengli, Marco
• Format: Article
• Language: English
• Subjects: 13/51; 14/32; 14/63; 631/67/589/466; 692/4028/67/589/466; Aged; Apoptosis; Apoptosis - genetics; Apoptosis - physiology; BAX protein; Bcl-2 protein; bcl-2-Associated X Protein - genetics; bcl-2-Associated X Protein - metabolism; Biopsy; Cancer surgery; Caspase 3 - genetics; Caspase 3 - metabolism; Caspase 9 - genetics; Caspase 9 - metabolism; Cell proliferation; Humanities and Social Sciences; Humans; Immunofluorescence; Immunohistochemistry; Irradiation; Ki-67 Antigen - genetics; Ki-67 Antigen - metabolism; Male; Middle Aged; multidisciplinary; p53 Protein; Prostate cancer; Prostatectomy; Prostatic intraepithelial neoplasia; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Radiation therapy; Science; Science (multidisciplinary); Statistical analysis; Tumor cells; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-64062-9

Radio-induced apoptosis is mediated by the activation of tumor protein p53, Bax and caspases. The purpose of this study was to investigate the early activation of this pathway in men receiving in vivo irradiation immediately before radical prostatectomy for locally advanced prostate cancer. We also investigated cell proliferation index (Ki-67), proto-oncogene (p53) and anti-apoptotic protein (Bcl-2) levels as potential predictive factors. We selected a homogeneous sample of 20 patients with locally advanced prostate cancer and candidate to radical prostatectomy. To assess the apoptotic pathways, Bax, is studied through immunofluorescence assay, before and after 12 Gy single dose intraoperative radiotherapy (IORT) to the prostate, on bioptic samples and on surgical specimens. Moreover, before and after IORT, Bcl-2, p53, and Ki-67 were also detected through immunohistochemistry. A count of positive Bax spots for immunofluorescence was performed on tumor cells, prostatic intraepithelial neoplasia (PIN), and healthy tissue areas before and after IORT. We also analyzed Caspases 3 and 9 expressions after IORT. Before IORT, Bcl-2 mean value in neoplastic cells was 2.23% ± 1.95, mean Ki-67 in neoplastic area was 4.5% ± 3.8, and p53 was 22.5% ± 6.8. After IORT, Bcl-2 mean value in neoplastic cells was 8.85 ± 8.92%, Ki-67 in neoplastic area was 7.8 ± 6.09%, and p53 was 24.9 ± 26.4%. After the irradiation, healthy areas expressed significantly lower levels of Bax (2.81 ± 1.69%) with respect to neoplastic cells (p