Profiling of somatostatin receptor subtype expression by quantitative PCR and correlation with clinicopathological features in pancreatic endocrine tumors.
OBJECTIVE
Pancreatic endocrine tumor (PET) presents variable clinical features. Five subtypes of somatostatin receptor (SSTR) are involved in hormone secretion and cell proliferation. In this paper, we explore the correlation between the SSTR subtype messenger RNA (mRNA) expression and clinicopathological features of PET.


METHODS
Twenty-one cases of PET and 5 cases of pancreatic adenocarcinomas (AC) were studied. Using total RNA extracted from paraffin sections and fresh tissues, SSTR subtype mRNA was quantified by real-time polymerase chain reaction. The hormones and MIB1 index were examined using immunohistochemical techniques.


RESULTS
The mRNA levels of SSTR1, SSTR2, SSTR3, and SSTR5 were high in PET compared with AC, whereas the expression of SSTR4 was low in PET and AC. Levels of each subtype did not vary with histological grades. Somatostatin receptor 2 levels in functioning tumors were slightly low compared with nonfunctioning tumors. Four distinct groups of PET were identified by hierarchical cluster analysis, and two of these groups showed reduced SSTR5 with elevation of MIB1 index.


CONCLUSIONS
The study showed a heterogeneous expression profile of SSTR subtype mRNA and the association of reduction in SSTR5 with high proliferative activity. Such profiling of SSTR subtypes may provide useful information on tumor biology and treatment of PET.
Nakayama
Yoshihito
Y
Departments of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan. ryuichi@cc.hirosaki-u.ac.jp
Wada
Ryuichi
R
Yajima
Nobuhisa
N
Hakamada
Ken-ichi
K
Yagihashi
Soroku
S
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D036361:Peptide Hormones / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D047368:Tumor Burden
D019394:Ki-67 Antigen; D036361:Peptide Hormones; 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