AUTHOR=Sigorski Dawid , Gulczyński Jacek , Sejda Aleksandra , Rogowski Wojciech , Iżycka-Świeszewska Ewa 

TITLE=Investigation of Neural Microenvironment in Prostate Cancer in Context of Neural Density, Perineural Invasion, and Neuroendocrine Profile of Tumors

JOURNAL=Frontiers in Oncology

VOLUME=Volume 11 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.710899

DOI=10.3389/fonc.2021.710899

ISSN=2234-943X

ABSTRACT=Cancer stroma contains neural compartment with specific component and action. Neural microenvironment processing includes among others axonogenesis, perineural invasion (PNI), neurosignalling, and tumor cell neural/ neuroendocrine differentiation. Growing data suggest that tumor- neural crosstalk plays important function in prostate cancer (PCa) biology. However, the mechanisms involved in PNI and axonogenesis, as well as their patho- clinical correlations in this tumor are not clear.
The present study was carried out on FFPE samples of 73 PCa and 15 benign prostate (BP) cases. Immunohistochemistry with neural markers PGP9.5, TH, and NFP was performed on constructed TMAs and selected tissue sections. The analysed parameters of tumor innervation included small nerve density (ND) measured on panneural marker (PGP9.5) and TH stained slides, as well assessment of PNI presence and morphology. The qualitative and topographic aspects were studied. In addition, expression of neuroendocrine marker chromogranin and NPY was assessed with dedicated indexes. Correlations of above parameters with patho- clinical data such as patients’ age, tumor stage, grade, angioinvasion, and ERG status were examined.
The study showed that innervation parameters differ between cancer and BP. The neural network in PCa reveals heterogeneity, and ND PGP9.5 in tumor is significantly lower than in its periphery. The density of sympathetic TH-positive fibres and its proportion to all fibres was lower in cancer than in periphery and BP samples. Perineural invasion occured in 76% of cases, usually multifocally, being more often in tumors with higher grade. NPY expression in PCa cells was common with its intensity often rising towards PNI. ERG+ tumors showed higher ND, more frequent PNI, and higher stage. Moreover, chromogranin- positive cells were more pronounced in PCa with higher NPY expression.
Performed analysis showed irregular axonal network in prostate cancer with higher neural density (panneural and adrenergic) in surroundings and invasive front. ND and PNI interrelated with NPY expression, neuroendocrine differentiation, and ERG status.
Above findings support new evidence for the presence of autocrine and paracrine interactions in prostate cancer neural microenvironment.