title: Inverse expression of somatostatin and CXCR4 chemokine receptors in gastroenteropancreatic neuroendocrine neoplasms of different malignancy.
abstract: BACKGROUND
  Somatostatin receptors (SSTR) are widely distributed in well-differentiated neuroendocrine neoplasms (NEN) and serve as primary targets for diagnostics and treatment. An overexpression of the chemokine receptor CXCR4, in contrast, is considered to be present mainly in highly proliferative and advanced tumors. Comparative data are still lacking, however, for neuroendocrine carcinomas (NEC).
  
  
  METHODS
  SSTR subtype (1, 2A, 3, 5) and CXCR4 expression was evaluated in G1 (n = 31), G2 (n = 47), and low (G3a; Ki-67: 21-49%; n = 21) and highly proliferative (G3b; Ki-67: >50%, n = 22) G3 (total n = 43) gastroenteropancreatic NEN samples by performing immunohistochemistry with monoclonal rabbit anti-human anti-SSTR and anti-CXCR4 antibodies, respectively, and was correlated with clinical data.
  
  
  RESULTS
  Both CXCR4 and SSTR were widely expressed in all tumors investigated. CXCR4 expression differed significantly between the G1 and G3 specimens and within the G3 group (G3a to G3b), and was positively correlated with Ki-67 expression. SSTR2A, in contrast, exhibited an inverse association with Ki-67. SSTR2A was highly expressed in G1 and G2 tumors, but was significantly less abundant in G3 carcinomas. Additionally, SSTR1 expression was higher in G3a than in G3b tumors.
  
  
  CONCLUSIONS
  We observed an elevation in CXCR4 and a decrease in SSTR2A expression with increasing malignancy. Interestingly, 23% of the G3 specimens had strong SSTR2A expression. Because CXCR4 was strongly expressed in highly proliferative G3 carcinomas, it is an interesting new target and needs to be validated in larger studies.
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 General and Visceral Surgery, Zentralklinik Bad Berka, Bad Berka, Germany.|Department of Pharmacology and Toxicology, Jena University Hospital, Friedrich Schiller University, Jena, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Träger
authors.affiliation: Institute of Pathology, University Hospital Tuebingen, Germany.
authors.forename: Maike
authors.initials: M
authors.lastname: Hoffmeister
authors.affiliation: Institute of Pathology, University Hospital Tuebingen, Germany.
authors.forename: Bence
authors.initials: B
authors.lastname: Sipos
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: Institute of Pathology and Cytology, Bad Berka, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Sänger
authors.affiliation: Department of Pharmacology and Toxicology, Jena University Hospital, Friedrich Schiller University, Jena, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schulz
authors.affiliation: Department of Pharmacology and Toxicology, Jena University Hospital, Friedrich Schiller University, Jena, Germany.
authors.forename: Amelie
authors.initials: A
authors.lastname: Lupp
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D049109:Cell Proliferation; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018358:Neuroendocrine Tumors / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D017481:Receptors, Somatostatin / Q000378:metabolism*; D013004:Somatostatin / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: C527276:CXCR4 protein, human; D019394:Ki-67 Antigen; D019718:Receptors, CXCR4; D017481:Receptors, Somatostatin; D013004:Somatostatin; C093733:somatostatin receptor 2
keywords: CXCR4; chemokine receptor; neuroendocrine carcinoma; neuroendocrine tumor; somatostatin receptor