title: Somatostatin receptor immunohistochemistry in neuroendocrine tumors: comparison between manual and automated evaluation.
abstract: BACKGROUND
  Manual evaluation of somatostatin receptor (SSTR) immunohistochemistry (IHC) is a time-consuming and cost-intensive procedure. Aim of the study was to compare manual evaluation of SSTR subtype IHC to an automated software-based analysis, and to in-vivo imaging by SSTR-based PET/CT.
  
  
  METHODS
  We examined 25 gastroenteropancreatic neuroendocrine tumor (GEP-NET) patients and correlated their in-vivo SSTR-PET/CT data (determined by the standardized uptake values SUVmax,-mean) with the corresponding ex-vivo IHC data of SSTR subtype (1, 2A, 4, 5) expression. Exactly the same lesions were imaged by PET/CT, resected and analyzed by IHC in each patient. After manual evaluation, the IHC slides were digitized and automatically evaluated for SSTR expression by Definiens XD software. A virtual IHC score "BB1" was created for comparing the manual and automated analysis of SSTR expression.
  
  
  RESULTS
  BB1 showed a significant correlation with the corresponding conventionally determined Her2/neu score of the SSTR-subtypes 2A (rs: 0.57), 4 (rs: 0.44) and 5 (rs: 0.43). BB1 of SSTR2A also significantly correlated with the SUVmax (rs: 0.41) and the SUVmean (rs: 0.50). Likewise, a significant correlation was seen between the conventionally evaluated SSTR2A status and the SUVmax (rs: 0.42) and SUVmean (rs: 0.62).
  
  
  CONCLUSIONS
  Our data demonstrate that the evaluation of the SSTR status by automated analysis (BB1 score), using digitized histopathology slides ("virtual microscopy"), corresponds well with the SSTR2A, 4 and 5 expression as determined by conventional manual histopathology. The BB1 score also exhibited a significant association to the SSTR-PET/CT data in accordance with the high affinity profile of the SSTR analogues used for imaging.
authors.affiliation: Department of General and Visceral Surgery, Zentralklinik Bad Berka Bad Berka, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kaemmerer
authors.affiliation: Department of Molecular Radiotherapy and Molecular Imaging, Center for PET, Zentralklinik Bad Berka Bad Berka, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Athelogou
authors.affiliation: Department of Pharmacology and Toxicology, Jena University Hospital Jena, Germany.
authors.forename: Amelie
authors.initials: A
authors.lastname: Lupp
authors.affiliation: Department of Pharmacology and Toxicology, Jena University Hospital Jena, Germany.
authors.forename: Isabell
authors.initials: I
authors.lastname: Lenhardt
authors.affiliation: Department of Pharmacology and Toxicology, Jena University Hospital Jena, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schulz
authors.affiliation: Department of General and Visceral Surgery, Zentralklinik Bad Berka Bad Berka, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Luisa
authors.affiliation: Department of General and Visceral Surgery, Zentralklinik Bad Berka Bad Berka, Germany.
authors.forename: Merten
authors.initials: M
authors.lastname: Hommann
authors.affiliation: Department of Nuclear Medicine, University Hospital Charité Berlin Germany ; Department of Molecular Radiotherapy and Molecular Imaging, Center for PET, Zentralklinik Bad Berka Bad Berka, Germany.
authors.forename: Vikas
authors.initials: V
authors.lastname: Prasad
authors.affiliation: Definiens AG Munich, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Binnig
authors.affiliation: Department of Molecular Radiotherapy and Molecular Imaging, Center for PET, Zentralklinik Bad Berka Bad Berka, Germany.
authors.forename: Richard Paul
authors.initials: RP
authors.lastname: Baum
mesh_terms: D000328:Adult; D000368:Aged; D057205:Automation, Laboratory; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D007150:Immunohistochemistry / Q000379:methods*; D007414:Intestinal Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D018358:Neuroendocrine Tumors / Q000175:diagnosis* / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000032:analysis*; D012984:Software; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D014057:Tomography, X-Ray Computed
chemical_list: D014408:Biomarkers, Tumor; D017481:Receptors, Somatostatin
keywords: PET/CT; Somatostatin receptor; immunohistochemistry; molecular imaging; neuroendocrine tumor