Intraprostatic sympathetic nerve count predicts prostate cancer recurrence
Perineural invasion (PNI) is commonly seen in prostate cancer but is not an independent predictor of biochemical recurrence (BCR). There is accumulating evidence to support a role of the autonomic nervous system in prostate cancer development and progression. We sought to investigate which autonomic nerve subtypes are involved in PNI in prostate cancer and how these relate to other clinical and pathological variables including BCR.
Histological evaluation of biorepository radical prostatectomy tissue from 141 men with known PNI was undertaken to identify a cohort of men for inclusion, balanced for recurrence. Hotspot analysis of 3 medium-power fields of intraprostatic PNI, serially stained with S100 plus AE1/AE3, tyrosine hydroxylase (TH) and neuronal nitric oxide synthase (nNOS) were examined to identify PNI, sympathetic and parasympathetic nerves respectively. Histological results were correlated with clinical data from a prospectively collected database.
98 men were included for analysis. Roughly equal numbers of participants had organ confined compared to locally advanced disease. 68% had Gleason 7 cancer. Overall 42% of the cohort experienced BCR, with follow-up time of 85 months (median) for men who did not recur. Mixed type bundles accounted for 71% of PNI nerves and 82% of non-PNI nerves. Total PNI nerve count and total pure sympathetic nerve counts both correlated with pT stage (p=0.0056 and p=0.025 respectively). Sympathetic non-PNI nerve count (HR 6.97, p=0.03), and non-adrenergic, non-nitrergic PNI nerve count (HR 10.56, p<0.005) both independently predicted BCR.</p>
Our work has revealed two independent predictors of BCR, and points towards a regulatory role of the autonomic nervous system in prostate cancer. A greater understanding of the mechanisms underpinning this relationship may translate into future therapeutic opportunities in prostate cancer.