Abstract

Abstract Background: Overexpression of breast cancer susceptibility gene 2 (BRCA2) in patients with prostate cancer is associated with a high Gleason score at diagnosis, poorly differentiated tumors, poor prognosis, and disease recurrence. Such aggressive tumors possess high iron storage which promotes inflammation, angiogenesis, and cell proliferation. Expression of iron progressively increases with cancer grade and stage. Purpose: This study evaluated the expression of BRCA2 protein and Iron expression in Gleason’s graded prostate cancer tissues, in a bid to determine the disease aggressiveness and mortality risk among Southern Nigerian men. Methods: In this retrospective study, 86 formalin-fixed paraffin-embedded prostate cancer tissues (diagnosed in 2018 and 2019) were reviewed using Gleason’s grading system. Tissues stained for iron and BRCA2 proteins using histochemical and immunohistochemical staining techniques, respectively. Staining intensity was scored using a scale of 0, +1, +2, and +3. For BRCA2 and Iron expressions, score 0 and +1 were considered negative while score +2 and +3 were considered positive. Pearson’s chi-square test was used to determine the association between Gleason’s grade and expression of BRCA2 and iron. Results: The prevalence of prostate cancer in the age groups of 50-59, 60-69, 70-79, 80-89, and 90-99 years was 10.8%, 32.4%, 40.5%, 13.5% and 2.7%, respectively. Using the Gleason’s grading pattern, the frequency of Grade (mean age in years) I, II, III, IV and V was 9.3% (70.25 ± 6.95), 16.3% (77.29 ± 6.23), 16.3% (75.57 ± 12.59), 25.6% (72.75 ± 7.80) and 32.6% (67.42 ± 9.76), respectively. Higher frequency of BRCA2 and Iron expression were observed in ≥G4 (37.5% and 72.7%) than in ≤G3 (versus 16.7% and 11.8%) at p= 0.191 and p< 0.001, respectively. The prevalence of BRCA2 negative and positive tissues was 65.1% and 34.9%, respectively whereas the prevalence of iron negative and positive tissues was 48.7% and 51.3%, respectively. There was an inverse relationship between tumour grade and age (p= 0.108), and direct relationships between tumour grade and BRCA2 (p= 0.059), tumour grade and iron (p= 0.000), BRCA2 and Iron expressions (p= 0.027), BRCA2 expression and age (p= 0.019), and Iron and age (p= 0.281). Patients with prostate cancer who are within the age group of 50-59 years and those with ≥G4 require close monitoring for improved survival. Conclusion: This study revealed a high prevalence of aggressive prostate cancer and suggests that there is a high mortality risk among Southern Nigerian men diagnosed with the disease. Citation Format: Jude O. Okoye, Vivian I. Ogbonnaya, Chiemeka M. Emeka, Okechi Obioma. Prostate cancer-related mortality risk assessment in a cohort of southern Nigerian men [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2247.

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