title: The prognostic and predictive value of sstr2-immunohistochemistry and sstr2-targeted imaging in neuroendocrine tumors.
abstract: OBJECTIVE
  Our aim was to assess the prognostic and predictive value of somatostatin receptor 2 (sstr2) in neuroendocrine tumors (NETs).
  
  
  METHODS
  We established a tissue microarray and imaging database from NET patients that received sstr2-targeted radiopeptide therapy with yttrium-90-DOTATOC, lutetium-177-DOTATOC or alternative treatment. We used univariate and multivariate analyses to identify prognostic and predictive markers for overall survival, including sstr2-imaging and sstr2-immunohistochemistry.
  
  
  RESULTS
  We included a total of 279 patients. In these patients, sstr2-immunohistochemistry was an independent prognostic marker for overall survival (HR: 0.82, 95 % CI: 0.67 - 0.99, n = 279, p = 0.037). In DOTATOC patients, sstr2-expression on immunohistochemistry correlated with tumor uptake on sstr2-imaging (n = 170, p < 0.001); however, sstr2-imaging showed a higher prognostic accuracy (positive predictive value: +27 %, 95 % CI: 3 - 56 %, p = 0.025). Sstr2-expression did not predict a benefit of DOTATOC over alternative treatment (p = 0.93).
  
  
  CONCLUSIONS
  Our results suggest sstr2as an independent prognostic marker in NETs. Sstr2-immunohistochemistry correlates with sstr2-imaging; however, sstr2-imaging is more accurate for determining the individual prognosis.
authors.affiliation: Institute of Pathology, University Hospital Basel, CH, Basel, Switzerland.|Institute of Nuclear Medicine, University Hospital Basel, CH, Basel, Switzerland.
authors.forename: Philippe
authors.initials: P
authors.lastname: Brunner
authors.affiliation: Institute of Nuclear Medicine, University Hospital Basel, CH, Basel, Switzerland.
authors.forename: Ann-Catherine
authors.initials: AC
authors.lastname: Jörg
authors.affiliation: Institute of Pathology, University Hospital Basel, CH, Basel, Switzerland.
authors.forename: Katharina
authors.initials: K
authors.lastname: Glatz
authors.affiliation: Institute of Pathology, University Hospital Basel, CH, Basel, Switzerland.
authors.forename: Lukas
authors.initials: L
authors.lastname: Bubendorf
authors.affiliation: Institute of Nuclear Medicine, University Hospital Bern, CH, 3010, Bern, Switzerland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Radojewski
authors.affiliation: Institute of Nuclear Medicine, University Hospital Bern, CH, 3010, Bern, Switzerland.
authors.forename: Maria
authors.initials: M
authors.lastname: Umlauft
authors.affiliation: Institute of Nuclear Medicine, University Hospital Basel, CH, Basel, Switzerland.|Institute of Nuclear Medicine, University Hospital Bern, CH, 3010, Bern, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Marincek
authors.affiliation: Institute of Nuclear Medicine, University Hospital Bern, CH, 3010, Bern, Switzerland.
authors.forename: Petar-Marko
authors.initials: PM
authors.lastname: Spanjol
authors.affiliation: Institute of Nuclear Medicine, University Hospital Bern, CH, 3010, Bern, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Krause
authors.affiliation: Institute of Nuclear Medicine, University Hospital Bern, CH, 3010, Bern, Switzerland.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Dumont
authors.affiliation: Division of Radiological Chemistry, University Hospital Basel, Basel, Switzerland.
authors.forename: Helmut R
authors.initials: HR
authors.lastname: Maecke
authors.affiliation: Institute of Nuclear Medicine, University Hospital Basel, CH, Basel, Switzerland.
authors.forename: Jan
authors.initials: J
authors.lastname: Müller-Brand
authors.affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, CH, Switzerland.|Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada.
authors.forename: Matthias
authors.initials: M
authors.lastname: Briel
authors.affiliation: Institute of Pathology, University Bern, Bern, Switzerland.
authors.forename: Anja
authors.initials: A
authors.lastname: Schmitt
authors.affiliation: Institute of Pathology, University Bern, Bern, Switzerland.
authors.forename: Aurel
authors.initials: A
authors.lastname: Perren
authors.affiliation: Institute of Nuclear Medicine, University Hospital Bern, CH, 3010, Bern, Switzerland. m.a.walter@gmx.net.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Walter
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging* / Q000378:metabolism; D015282:Octreotide / Q000009:adverse effects / Q000031:analogs & derivatives*; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D011237:Predictive Value of Tests; D019275:Radiopharmaceuticals / Q000009:adverse effects*; D017481:Receptors, Somatostatin / Q000378:metabolism
chemical_list: C504257:177Lu-octreotide, DOTA(0)-Tyr(3)-; D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin; C574734:SSTR2 protein, human; C496730:90Y-octreotide, DOTA-Tyr(3)-; D015282:Octreotide
keywords: Individualized therapy; Metabolic therapy; PRRT; Tailored therapy; Targeted therapy