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Neuroendocrine Differentiation in Prostate Cancer

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Book cover Prostate Cancer: Shifting from Morphology to Biology

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Abstract

Neuroendocrine differentiation (ND) is widely observed in prostate cancer (PC). Its role in clinical practice is controversial, but preclinical and clinical evidences underline the association of ND with poor prognosis in PC patients. Neuroendocrine (NE) cells could condition the PC progression, mainly stimulating the PC exocrine neoplastic cells proliferation through the production of paracrine growth factors. Thus, the castrated adapted neoplastic cells are favored to outgrowth through an androgen receptor independent mechanism. Moreover proportion of NE cells in PC increases because of tumor treatment, mainly androgen deprivation therapy, enormously amplifying the promotion of the PC exocrine component growth stimulated by neuroendocrine paracrine growth factors.

This chapter provides an overview of the most relevant clinical studies demonstrating a significant correlation between ND and PC behavior, indicating that ND could represent a prognostic parameter in PC, and strongly suggesting that NE cells in a castrate resistant patients could be targeted through specific treatment.

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Abbreviations

ND:

Neuroendocrine differentiation

NE:

Neuroendocrine

PC:

Prostate cancer

PSA:

The prostate specific antigen

CGA:

ChromograninA

NSE:

Neuron-specific enolase

VIP:

Vasoactive intestinal peptide

GRP:

Bombesin/gastrin releasing peptide

aHCG:

Alpha-human chorionic gonadotropin

PTHrP:

Parathyroid hormonerelated protein

VEGF:

Vascular endothelial growth factor

SCC:

Small cell carcinomas

PIN:

Prostatic intraepithelial neoplasia

AMACR:

Alpha-methylacyl-CoA racemase

ADT:

Androgen deprivation therapy

uPA:

Urokinase-type plasminogen activator

PAI-1:

Plasminogen activator inhibitor-1

MMP:

Metalloprotease

MDV:

Microvascular density

MAPKs:

Mitogen activated protein kinases

PKA:

Cyclic AMP-dependent protein kinase

PI3K:

Phosphatidylinositol 3-kinase

CDK:

Cyclin-dependent kinase

CGB:

Chromogranin B

CGC:

Chromogranin C

ProGRP:

Progastrin-releasing peptide

BPH:

Prostatic hyperplasia

PS:

Performance status

PET:

Positron emission tomography

FDG:

F18-fluorodeoxyglucose

DTPA:

Diethylenetriaminepentaacetic acid

DTX:

Docetaxel

OS:

Overall survival

TTP:

Time to progression

DOTA:

1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid

PTP:

Protein tyrosine phosphatase

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Authors and Affiliations

  1. Department of Laboratory Medicine, National Institute of Tumors Fondazione “G. Pascale”, Via Mariano Semmola 1, 80131, Naples, Italy

    Renato Franco

  2. Department of Experimental Medicin, Second University of Naples, Via Costantinopoli 16, 80138, Naples, Italy

    Paolo Chieffi

  3. Department of Urogynecologic Oncology, National Institute of Tumors Fondazione “G. Pascale”, Via Mariano Semmola 1, 80131, Naples, Italy

    Sisto Perdonà & Gaetano Facchini

  4. Department of Biochemistry and Biophysics, Second University of Naples, Via Costantinopoli, 16, 80138, Naples, Italy

    Michele Caraglia

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  5. Michele Caraglia
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Correspondence to Renato Franco .

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  1. Biomedical Advanced Sciences Pathology Section, University Federico II of Naples, Naples, Italy

    Stefania Staibano

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Franco, R., Chieffi, P., Perdonà, S., Facchini, G., Caraglia, M. (2013). Neuroendocrine Differentiation in Prostate Cancer. In: Staibano, S. (eds) Prostate Cancer: Shifting from Morphology to Biology. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7149-9_5

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