title: Comparing of IRS and Her2 as immunohistochemical scoring schemes in gastroenteropancreatic neuroendocrine tumors.
abstract: Neuroendocrine tumors (NET) are known for an overexpression of somatostatin receptors (SSTR). In light of very few and partially contradictory publications, the present study aims to achieve a definite immunohistochemical (IHC) quantification and assessment of the distribution of all five SSTR-subtypes on NET and to evaluate an implementable scoring system, comparing the immunoreactive score of Remmele and Stegner (IRS) to the Her2-score. In 21 patients 40 different tumor tissues were IHC analysed using polyclonal antibodies for SSTR1 and 3-5 and the monoclonal antibody UMB-1 for SSTR2A. SSTR expression was quantitatively evaluated according to HER2-score and IRS, correlated among each other and to the maximum standardized uptake value (SUVmax) in tumor lesions as measured by PET/CT using 68Ga-DOTA-NOC.
  
  
  RESULTS
  According to the IRS, the expression of SSTR2A and 3 predominated equally with 84%, followed by SSTR4 (44%) and SSTR1 and 5 (32%). With the Her2-scoring system the most frequent subtype was found to be SSTR2A (68%), followed by SSTR3 (64%), SSTR1 (44%), SSTR5 (40%), and SSTR4 (36%). The IRS-classification and the Her2-score were found to be statistically comparable, and their correlation is highly significant for each SSTR assessment (p<0.01).
  
  
  CONCLUSIONS
  The results of the analyses revealed heterogeneous expression patterns. SSTR2A and 3 were highly expressed, demonstrating the importance of SSTR for diagnostics and therapy. Relatively high frequency of SSTR3 and 4 on NET give reasons to try pansomatostatin analogues for therapy rather than concentrating only on the SSTR2A. Statistically, none of the immunohistochemical scores was superior. However, due the heterogeneity of the cytoplasmic staining justice we propose the IRS as a uniform scoring scheme for IHC NET diagnostic.
authors.affiliation: Department of General and Visceral Surgery, Zentralklinik Bad Berka, Bad Berka, Germany. Daniel. Kaemmerer@zentralklinik.de
authors.forename: Daniel
authors.initials: D
authors.lastname: Kaemmerer
authors.forename: Luisa
authors.initials: L
authors.lastname: Peter
authors.forename: Amelie
authors.initials: A
authors.lastname: Lupp
authors.forename: Stefan
authors.initials: S
authors.lastname: Schulz
authors.forename: Jörg
authors.initials: J
authors.lastname: Sänger
authors.forename: Richard Paul
authors.initials: RP
authors.lastname: Baum
authors.forename: Vikas
authors.initials: V
authors.lastname: Prasad
authors.forename: Merten
authors.initials: M
authors.lastname: Hommann
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D004067:Digestive System Neoplasms / Q000737:chemistry* / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D064847:Multimodal Imaging; D018358:Neuroendocrine Tumors / Q000737:chemistry* / Q000000981:diagnostic imaging / Q000473:pathology; D009942:Organometallic Compounds; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D011379:Prognosis; D019275:Radiopharmaceuticals; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D017481:Receptors, Somatostatin / Q000032:analysis*; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D018719:Erb-b2 Receptor Tyrosine Kinases; D017481:Receptors, Somatostatin; C504894:68Ga-DOTANOC; C508053:ERBB2 protein, human