title: SSTR5 P335L monoclonal antibody differentiates pancreatic neuroendocrine neuroplasms with different SSTR5 genotypes.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Guisheng
authors.initials: G
authors.lastname: Zhou
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Gingras
authors.forename: Shi-He
authors.initials: SH
authors.lastname: Liu
authors.forename: Robbi
authors.initials: R
authors.lastname: Sanchez
authors.forename: Dean
authors.initials: D
authors.lastname: Edwards
authors.forename: David
authors.initials: D
authors.lastname: Dawson
authors.forename: Kurt
authors.initials: K
authors.lastname: Christensen
authors.forename: Giovanni
authors.initials: G
authors.lastname: Paganelli
authors.forename: Richard
authors.initials: R
authors.lastname: Gibbs
authors.forename: William
authors.initials: W
authors.lastname: Fisher
authors.forename: Francis C
authors.initials: FC
authors.lastname: Brunicardi
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D018358:Neuroendocrine Tumors / Q000175:diagnosis / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017481:Receptors, Somatostatin / Q000235:genetics* / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D017481:Receptors, Somatostatin; C094573:somatostatin receptor 5