Biological correlates of prostate cancer perineural invasion diameter

Perineural invasion is a symbiotic relationship between cancer cells and nerves and is most frequently seen in "neurotropic" cancers such as prostate cancer. It results in increased perineural space cancer cell growth and decreased apoptosis and induces nerve growth. Tissue microarrays were constructed from 640 radical prostatectomy specimens with prostate cancer. The perineural diameter was measured as previously described. Multiple biomarkers have been previously performed on this tissue microarray cohort, and all data were kept in the same database. The biomarker results database was queried for correlations between perineural invasion diameter and tissue biomarkers. Increased perineural invasion diameter correlated with increased proliferation of prostate cancer cells and with apoptosis. It also correlated with proteins involved in survival pathways such as nuclear factor κB, c-Myc, phosphorylated AKT, and its downstream effector FHKR, but not with GSK. Unlike nerve density, it did not correlate with decreased PTEN expression. Increased perineural invasion diameter was associated with higher levels of hormonal receptors such as androgen receptor, but not estrogen receptor. Also associated with perineural invasion diameter were coregulators and corepressors including SRC1 and TIF2. Perineural invasion diameter had the strongest correlation with tumor volume (ρ = 0.579, P = .000), not identified with nerve density. These data demonstrate that perineural invasion has the same biologic correlations as neural density. However, we found a distinct and very strong correlation with increased tumor volume. These data confirm that perineural invasion is the ultimate and most successful interaction between cancer cells and nerve fibers, resulting in increased tumor growth.