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Pathol Res Pract. 2018 Jun;214(6):848-856. doi: 10.1016/j.prp.2018.04.015. Epub 2018 Apr 26.

Expression of neuroendocrine differentiation markers in lethal metastatic castration-resistant prostate cancer.

Author information

1
Prostate Cancer Research Center, Faculty of Medicine and Life Sciences and BioMediTech Institute, University of Tampere, Tampere, FI-33014, Finland. Electronic address: sainio.miika.s@student.uta.fi.
2
Prostate Cancer Research Center, Faculty of Medicine and Life Sciences and BioMediTech Institute, University of Tampere, Tampere, FI-33014, Finland. Electronic address: tapio.visakorpi@uta.fi.
3
Prostate Cancer Research Center, Faculty of Medicine and Life Sciences and BioMediTech Institute, University of Tampere, Tampere, FI-33014, Finland; Department of Pathology, Tampere University Hospital, Fimlab Laboratories, Tampere, Finland. Electronic address: teemu.tolonen@fimlab.fi.
4
Department of Pathology, Tampere University Hospital, Fimlab Laboratories, Tampere, Finland. Electronic address: joanna.ilvesaro@fimlab.fi.
5
Prostate Cancer Research Center, Faculty of Medicine and Life Sciences and BioMediTech Institute, University of Tampere, Tampere, FI-33014, Finland. Electronic address: g.steven.bova@uta.fi.

Abstract

Neuroendocrine differentiation (NED) is a common phenomenon in prostate cancer, and it has been associated with poor prognosis in some studies of primary prostate cancer. Incidence and patterns of NED in metastatic prostate cancer sites have not been examined widely. In this study, we studied expression of three commonly used markers of NED (chromogranin A, neuron specific enolase and synaptophysin) in 89 metastases from 31 men that died of castration-resistant prostate cancer and underwent rapid autopsy, and in 89 hormone-naïve primary tumors removed by radical prostatectomy. In addition, we examined NED association with androgen receptor, ERG and Ki-67 expression in metastatic tumor sites. Morphologically, 1 of 31 cases was classified as small cell carcinoma, and the remaining 30 were classified as usual prostate adenocarcinoma using a recently proposed classification of prostate cancers with NED. Metastases showed more expression of neuron specific enolase and synaptophysin compared to prostatectomies (6.3% of cells vs. 1.0%, p < 0.001 and 4.0% vs. 0.4%, p < 0.001, respectively). At least focal expression of one of the markers was seen in 78% of metastases. Strong expression was relatively uncommon, seen in 3/89 (chromogranin A), 8/89 (neuron specific enolase), and 5/89 (synaptophysin) metastases. Expression of chromogranin A and synaptophysin correlated with each other (r = 0.64, p < 0.001), but expression of neuron specific enolase did not correlate with the two other markers. Extent of NED varied significantly between different metastatic sites in individual patients. Absent androgen receptor expression was associated with strong expression of chromogranin A (p = .02) and neuron specific enolase (p = .02), but not with focal expression of any marker. No clear association was found between expression of NE markers and ERG or Ki-67. In conclusion, NED is a common and heterogeneous phenomenon in metastatic, castration-resistant prostate cancer. NED is more often present in castration-resistant prostate cancer compared to hormone-naïve disease, and it is associated with androgen receptor negativity. More research is needed to understand significance of NED in the progression of prostate cancer.

KEYWORDS:

Androgen receptor; Castration-resistant prostate cancer; Chromogranin A; Immunohistochemistry; Neuroendocrine differentiation; Synaptophysin

PMID:
29728311
DOI:
10.1016/j.prp.2018.04.015
[Indexed for MEDLINE]

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