Inverse expression of somatostatin and CXCR4 chemokine receptors in gastroenteropancreatic neuroendocrine neoplasms of different malignancy
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Daniel Kaemmerer1, Tina Träger1,2, Maike Hoffmeister3, Bence Sipos3, Merten Hommann1, Jörg Sänger4, Stefan Schulz2, Amelie Lupp2
1Department of General and Visceral Surgery, Zentralklinik Bad Berka, Bad Berka, Germany
2Department of Pharmacology and Toxicology, Jena University Hospital, Friedrich Schiller University, Jena, Germany
3Institute of Pathology, University Hospital Tuebingen, Germany
4Institute of Pathology and Cytology, Bad Berka, Germany
Daniel Kaemmerer, e-mail: Daniel.Kaemmerer@zentralklinik.de
Keywords: somatostatin receptor, neuroendocrine tumor, neuroendocrine carcinoma, chemokine receptor, CXCR4
Received: April 13, 2015 Accepted: July 03, 2015 Published: July 14, 2015
Introduction: 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.
Conclusion: 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.
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