Somatostatin receptor subtypes in hormone-refractory
(castration-resistant) prostatic carcinoma
Roberta Mazzucchelli1,*, Doriana Morichetti1,*, Marina Scarpelli1, Aldo V Bono1, Antonio Lopez-Beltran2,
Liang Cheng3, Ziya Kirkali4and Rodolfo Montironi1
(HR) prostate cancer (PCa). Five SSTRs were evaluated immunohistochemically in 20 radical prostatectomies (RPs) with Gleason
score (GS) 31356 PCa, in 20 RPs with GS 41458 and 41559 PCa, and 20 transurethral resection of the prostate specimens with
HR PCa. The mean values in the cytoplasm (all five SSTRs were expressed), membrane (only SSTR3 and SSTR4 were expressed) and
nuclei (only SSTR4 and SSTR5 were expressed) of the glands in HR PCa were 20–70% lower than in the other two groups, the
differences being statistically significant. All five SSTRs were expressed in the smooth muscle and endothelial cells of HR PCa, the
mean values being lower than in the other two groups. In conclusion, this study expands our knowledge on the expression and
localisation of five SSTRs in the various tissue components in the HR PCa compared with hormone-sensitive PCa.
Asian Journal of Andrology (2011) 13, 242–247; doi:10.1038/aja.2010.100; published online 13 December 2010
Keywords: hormone-refractory prostate cancer; prostate cancer progression; prostatic adenocarcinoma; somatostatin receptors
Current treatment for localized, early-stage prostate cancer (PCa)
involves either surgery (radical prostatectomy (RP)) or radiation,
treatment for patients with hormone-sensitive metastatic disease is to
deplete testosterone concentrations with a gonadotropin-releasing
hormone analogue and antagonist, or surgical orchiectomy, either
alone or in combination with an anti-androgen. The results are pre-
dictable: an initial decline in serum prostate-specific antigen (PSA),
the secreted protein product of an androgen receptor-regulated gene,
followed by tumour regression. After a period of quiescence, PSA
concentrations rise, indicating androgen receptor reactivation, fol-
lowed by disease progression and the development of disease-related
symptoms. This phase of the illness represents a transition to
hormone-refractory (HR) prostatic adenocarcinoma. The median
options available, comprising chemotherapy, are only to be seen as
androgen deprivation was initially found to produce only marginal
responses,2but is now being re-evaluated with interest as new agents
and better supportive care become available.3Nevertheless, palliation
still remains the primary goal of current chemotherapy, and overall
response rates are low and associated with general toxicity. To over-
come the problem of toxicity, attempts have been made to achieve
site-specific drug delivery and improve the therapeutic index.
Targeted chemotherapy using potent cytotoxic radicals conjugated
to carrier molecules, such as antibodies4,5or analogues of peptide
hormones,6which can be specifically recognized by tumour cells,
improves the therapy of HR PCa.
Among the analogues of peptide hormones, somatostatin (SST)
analogues have gained the most attention because of their antineo-
plasticeffects,such asdecreased tumourcellgrowthandangiogenesis,
as well as an increased cancer cell apoptosis.7These inhibitory effects
by tumours expressing SST receptors (SSTRs), whereas the latter may
play a role in the regulation of SSTR-positive cells by modulating the
effect of their growth stimuli, including the inhibition of secretion of
growth-promoting factors, such as insulin-like growth factor-1, epi-
dermal growth factor and transforming growth factor, all of which
specifically regulate tumour growth.7
Previous studies from our group evaluated the five SSTRs in conven-
tional PCa, androgen-dependent PCa with neuroendocrine (NE) differ-
entiation and androgen-dependent PCa following androgen ablation
therapy.8–10These investigations pointed out that typing SSTR express-
ion and localisation could be of great relevance in SST analogue-based
treatment approaches. No information is available in the current litera-
ture on SSTR subtype expression and localisation in HR PCa.
The aim of the current study was to examine immunohistochemi-
cally the expression and localisation of the five SSTRs in HR PCa.
*These authors contributed equally to this work.
Correspondence: Dr R Montironi (email@example.com)
Received: 26 May 2010; Revised: 5 July 2010; Accepted: 30 July 2010; Published online: 13 December 2010
University Hospital and Faculty of Medicine, Cordoba 14001, Spain;3Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN
46202, USA and4Department of Urology, School of Medicine, Dokuz Eylu ¨l University, Izmir 35010, Turkey
Asian Journal of Andrology (2011) 13, 242–247
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SSTRs in hormone-refractory prostate cancer
R Mazzucchelli et al
Asian Journal of Andrology