Testing novel histological markers for fibrosis in Benign Prostatic Hyperplasia (BPH)
Abstract
Introduction: BPH often presents with prostatic fibrosis, which is the formation of fibrous tissue within the prostate due to aging or inflammation. Staining for fibrosis using a COL1A1 antibody is common; however, the baseline level of Collagen-I is high in the prostate, making it difficult to establish fibrotic grades. The aim of this study is to identify a more quantitative marker for visualizing prostatic fibrosis via immunohistochemistry (IHC), and uncover any correlations between optical density and patient data.
Methods: BPH patients were consented at Urology of Virginia and received Holmium Laser Enucleation of the Prostate (HoLEP) surgery at Sentara Norfolk General. Tissues from 10 patients were selected for IHC. Antibodies for three markers of fibrosis: COL1A1, Lumican, and Decorin, were optimized and then applied. The average staining intensity for each antibody was calculated using InForm Software (Akoya). Additional patient data regarding age, race, BPH medication, smoking status, prostate specific antigen (PSA) levels, and prostate size were accessed via Epic Hyperspace and organized in RedCap. Prism software was used to correlate patient data with staining intensity.
Results: Variability in optical density is associated with a better indication for the use as a biomarker in our experiments. Interestingly, COL1A1 showed the highest variability, followed by decorin and lumican. Although no statistically significant correlations were found in regards to prostate size, COL1A1 displayed the lowest P value of 0.1210, and the highest R2 value with 0.3079. Mann-Whitney test showed no statistically significant difference in COL1A1 intensity between Caucasian and African-American patients. BPH treatment and smoking status was also not associated with staining intensity of the antibodies tested.
Conclusion: Our studies indicate that COL1A1 performs best to indicate the degree of prostatic fibrosis. We found a trend for inverse correlation between prostate volume and COL1A1 density, which corroborates earlier suggestions about the relationship between prostate size and fibrosis. Our future experiments will focus on increasing the sample size of tissues assessed to provide statistically significant proof of this correlation.