Differential expression of somatostatin receptor subtypes in hepatocellular carcinomas.
OBJECTIVE
Somatostatin analogues inhibit cell proliferation by stimulation of distinct somatostatin receptor (SSTR) subtypes. In recent years, these compounds have been introduced into the therapy of advanced hepatocellular carcinoma (HCC). The efficacy of this treatment is under debate due to the controversial results of clinical trials. Despite the widespread clinical use of somatostatin analogues in HCC, little is known about the expression of each of the five SSTRs in these tumors.


METHODS
We analyzed the expression of SSTR subtypes in 56 HCCs by immunohistochemistry using subtype-specific antibodies. Six of the samples were also investigated by RT-PCR using subtype-specific oligonucleotide primers.


RESULTS
HCCs display differential, individual expression patterns as well as variable expression levels for SSTRs. The overall expression rate of SSTR1, SSTR2, SSTR3, SSTR4, and SSTR5 is 46, 41, 64, 0, and 75%, respectively. No significant correlation was observed between SSTR expression and tumor stage, differentiation, histological tumor type, or underlying liver disease.


CONCLUSIONS
Individual patterns and levels of SSTR expression might determine the response to treatment with somatostatin analogues in HCC. Selective treatment of these tumors based on the analysis of SSTR subtype expression might lead to an increase in response rates.
Bläker
Michael
M
Medizinische Klinik I, Zentrum für Innere Medizin, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. blaeker@uke.uni-hamburg.de
Schmitz
Michael
M
Gocht
Andreas
A
Burghardt
Sylvia
S
Schulz
Martina
M
Bröring
Dieter C
DC
Pace
Andrea
A
Greten
Heiner
H
De Weerth
Andreas
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D002648:Child; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008099:Liver / Q000473:pathology / Q000502:physiology; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D008565:Membrane Proteins; D008875:Middle Aged; D017481:Receptors, Somatostatin / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D008565:Membrane Proteins; D017481:Receptors, Somatostatin; C103631:somatostatin receptor 3; C098681:somatostatin receptor subtype-4; C101130:somatostatin receptor type 1; C094573:somatostatin receptor 5; C093733:somatostatin receptor 2