Biologic correlates and significance of axonogenesis in prostate cancer.
Cancer-related axonogenesis and neurogenesis are recently described biologic phenomena. Our previously published data showed that nerve density and the number of neurons in the parasympathetic ganglia are increased in prostate cancer (PCa) and associated with aggressive disease. Tissue microarrays were constructed from 640 radical prostatectomy specimens with PCa. Anti-protein gene product 9.5 (PGP 9.5) antibodies were used to identify and quantify nerve density. Protein expression was objectively analyzed using deconvolution imaging, image segmentation, and image analysis. Data were correlated with clinicopathological variables and tissue biomarkers available in our database. Nerve density, as measured by PGP 9.5 expression, had a weak but significant positive correlation with the lymph node status (ρ = 0.106; P = .0275). By Cox univariate analysis, PGP 9.5 was a predictor of time to biochemical recurrence, but not on multivariate analysis. Increased nerve density correlated with increased proliferation of PCa cells. It also correlated with expression of proteins involved in survival pathways (Phosphorylated alpha serine/threonine-protein kinase, NFκB, GSK-2, PIM-2, c-Myc, SKP-2, SRF, P27n, PTEN), with increased levels of hormonal regulation elements (androgen receptor, estrogen receptor α), and coregulators and repressors (SRC-1, SRC-2, AIB-1, DAX). Axonogenesis is a recently described phenomenon of paramount importance in the biology of PCa. Although the degree of axonogenesis is predictive of aggressive behavior in PCa, it does not add to the information present in current models on multivariate analysis. We present data that corroborate that axonogenesis is involved in biologic processes such as proliferation of PCa, through activation of survival pathways and interaction with hormonal regulation.
Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030.
Adriana
A
Olar
Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030.
Dandan
D
He
Department of Internal Medicine, Sinai-Grace Hospital and Wayne State University, Detroit, MI 48235.
Diego
D
Florentin
Department of Pathology and Laboratory Medicine, The University of Texas Health Sciences Center at Houston, Medical School, Houston, TX 77030.
Yi
Y
Ding
Department of Pathology and Laboratory Medicine, The University of Texas Health Sciences Center at Houston, Medical School, Houston, TX 77030. Electronic address: Gustavo.E.Ayala@uth.tmc.edu.
Gustavo
G
Ayala
D001369:Axons / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D055495:Neurogenesis / Q000502:physiology*; D011379:Prognosis; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
C482860:UCHL1 protein, human; D043222:Ubiquitin Thiolesterase
Axonogenesis; Nerve density; PGP 9.5; Prostate cancer