Biologic Significance of Axonogenesis in Prostate Cancer Measured by PGP 9.5
Dandan He, Yi Ding, Anna Frolov, Michael Ittmann, Gustavo Ayala. Baylor College of Medicine, Houston, TX; Diana Helis Henry Medical Research Foundation, New Orleans, LA; University of Texas Health Sciences Center Medical School, Houston, TX
Background: Cancer induced axonogenesis and neurogenesis is a recently described biologic phenomenon. Our previously published data showed that nerve density in PCa and the number of neurons in the parasympathetic ganglia are increased with prostate cancer (PCa) progression. Protein gene product 9.5 (PGP 9.5) is a member of the ubiquitin hydrolase family, confined to the cytoplasm of the nerves and neurons.
Design: Tissue microarrays were constructed from 435 radical prostatectomy specimens with PCa. Anti-PGP 9.5 antibodies were used to identify and quantify nerve density. Protein expression was objectively analyzed using computerized digital image analysis and was correlated with clinico-pathological variables and tissue biomarkers available in our database.
Results: Only lymph node status had a weak but significant, positive correlation with nerve density (ρ=0.106; p=0.0275). By Cox univariate analysis, PGP 9.5 was a predictor of time to biochemical recurrence (p=0.05). However, it was not an independent predictor of biochemical recurrence on multivariate analysis. Higher nerve density correlated with higher proliferation of PCa cells Ki67 (ρ=0.186, p=0.0019). It also correlated positively with expression of proteins involved in survival pathways such as p-AKT, pNFKB p536, GSK2, PIM2, CMYC, SKP2, SRF, P27n, and negatively with PTEN. Increased nerve density correlated with increased levels of hormonal regulation elements: AR, ER Alpha; and co regulators and repressors: SRC1, TIF2, AIB-1, DAX.
Conclusions: Increased axono-neurogenesis, as demonstrated by PGP 9.5 expression is associated with aggressiveness and disease progression in prostate cancer. These data suggest that nerve cancer biology is paramount in prostate cancer.
Category: Genitourinary (including renal tumors)
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 138, Wednesday Afternoon