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Int J Clin Exp Pathol 2012;5(3):187-194

Original Article
Comparing of IRS and Her2 as immunohistochemical scoring schemes in
gastroenteropancreatic neuroendocrine tumors

Daniel Kaemmerer, Luisa Peter, Amelie Lupp, Stefan Schulz, Jorg Sanger, Richard Paul Baum, Vikas Prasad, Merten Hommann

Department of General and Visceral Surgery, Zentralklinik Bad Berka, Bad Berka, Germany; Department of Pharmacology and Toxicology,
University of Jena, Jena, Germany; Laboratory of Pathology and Cytology, Bad Berka, Germany; Department for Molecular Radiotherapy and
Center for Molecular Imaging (PET/CT), ENETS Center of Excellence, Zentralklinik Bad Berka, Bad Berka, Germany; Department of Nuclear
Medicine, University Hospital Charité, Berlin, Germany. *Both authors contributed equally to the manuscript.

Received March 4, 2012; accepted March 17, 2012; Epub March 25, 2012; Published March 30, 2012

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 others 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). Conclusion: 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 superiorly. (IJCEP1203003

Keywords: Gastroenteropancreatic neuroendocrine tumors, somatostatin receptors, UMB-1 antibody, immunohistochemistry, IRS, Her2-score

Address all correspondence to:
Dr. Daniel Kaemmerer
Department of General and Visceral Surgery
Zentralklinik Bad Berka GmbH
Robert-Koch-Allee 9, 99437
Bad Berka, Germany.
Tel: + 49 36458 52701; Fax: + 49 36458 53536
E-mail: Daniel. Kaemmerer@zentralklinik.de