SSTR5 P335L monoclonal antibody differentiates pancreatic neuroendocrine neuroplasms with different SSTR5 genotypes.

TitleSSTR5 P335L monoclonal antibody differentiates pancreatic neuroendocrine neuroplasms with different SSTR5 genotypes.
Publication TypeJournal Article
Year of Publication2011
AuthorsZhou, G, Gingras, M-C, Liu, S-H, Sanchez, R, Edwards, D, Dawson, D, Christensen, K, Paganelli, G, Gibbs, R, Fisher, W, Brunicardi, FC
JournalSurgery
Volume150
Issue6
Pagination1136-42
Date Published2011 Dec
ISSN1532-7361
KeywordsAntibodies, Monoclonal, Murine-Derived, Blotting, Western, Cell Line, Tumor, Genotype, Humans, Immunohistochemistry, Neuroendocrine Tumors, Pancreatic Neoplasms, Polymorphism, Single Nucleotide, Receptors, Somatostatin, Reverse Transcriptase Polymerase Chain Reaction
Abstract

BACKGROUND: Somatostatin receptor type 5 (SSTR5) P335L is a hypofunctional, single nucleotide polymorphism of SSTR5 with implications in the diagnostics and therapy of pancreatic neuroendocrine neoplasms. The purpose of this study is to determine whether a SSTR5 P335L-specific monoclonal antibody could sufficiently differentiate pancreatic neuroendocrine neoplasms (PNENs) with different SSTR5 genotypes.METHODS: Cellular proliferation rate, SSTR5 mRNA level, and SSTR5 protein level were measured by performing MTS assay, a quantitative reverse transcription polymerase chain reaction study, Western blot analysis, and immunohistochemistry, respectively. SSTR5 genotype was determined with the TaqMan SNP Genotyping assay (Applied Biosystems, Foster City, CA).RESULTS: We found that the SSTR5 analogue RPL-1980 inhibited cellular proliferation of CAPAN-1 cells more than that of PANC-1 cells. Only PANC-1 (TT) cells, but not CAPAN-1 (CC) cells expressed SSTR5 P335L. In 29 white patients with PNENs, 38% had a TT genotype for SSTR5 P335L, 24% had a CC genotype for WT SSTR5, and 38% hada CT genotype for both SSTR5 P335L and WT SSTR5. Immunohistochemistry using SSTR5 P335L monoclonal antibody detected immunostaining signals only from the neuroendocrine specimens with TT and CT genotypes, but not those with CC genotypes.CONCLUSION: A SSTR5 P335L monoclonal antibody that specifically recognizes SSTR5 P335L but not WT SSTR5 could differentiate PNENs with different SSTR5 genotypes, thereby providing a potential tool for the clinical diagnosis of PNEN.

DOI10.1016/j.surg.2011.09.044
Alternate JournalSurgery
PubMed ID22136833
PubMed Central IDPMC3233698
Grant ListR01 DK46441 / DK / NIDDK NIH HHS / United States
R56 DK046441 / DK / NIDDK NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
R56 DK046441-15A1 / DK / NIDDK NIH HHS / United States
R01 DK046441 / DK / NIDDK NIH HHS / United States