Differential expression and prognostic value of the chemokine receptor CXCR4 in bronchopulmonary neuroendocrine neoplasms
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Daniel Kaemmerer1,*, Christiane Reimann2,*, Elisa Specht2, Ralph M. Wirtz3, Manal Sayeg4, Richard P. Baum5, Stefan Schulz2 and Amelie Lupp2
1 Department of General and Visceral Surgery, Zentralklinik Bad Berka, Bad Berka, Germany
2 Department of Pharmacology and Toxicology, Jena University Hospital, Jena, Germany
3 Stratifyer Molecular Pathology GmbH, Cologne, Germany
4 Department of Internal Medicine, Gastroenterology and Endocrinology, Zentralklinik Bad Berka, Bad Berka, Germany
5 Department of Molecular Radiotherapy and Molecular Imaging, Center for PET/CT, Zentralklinik Bad Berka, Bad Berka, Germany
* These authors contributed equally to this work
Daniel Kaemmerer, email:
Keywords: lung cancer, neuroendocrine neoplasm (NEN), small cell lung cancer (SCLC), CXCR4, immunohistochemistry (IHC)
Received: November 01, 2014 Accepted: December 24, 2014 Published: December 30, 2014
Introduction: For many tumors, the overexpression of the chemokine receptor CXCR4 is associated with increased malignancy and poor patient outcomes. However, comprehensive data for neuroendocrine neoplasms of the lung are still lacking.
Methods: CXCR4 expression was evaluated in a panel of bronchopulmonary neuroendocrine neoplasms (BP-NEN) comprising typical carcinoids (n = 26), atypical carcinoids (n = 30), and small cell lung cancers (SCLC, n = 34). Samples were analyzed by immunohistochemistry using the novel monoclonal rabbit anti-human CXCR4 antibody UMB-2 and by qRT-PCR. The expression was correlated with clinical data and overall patient survival.
Results: CXCR4 was predominantly localized at the plasma membrane of the tumor cells. CXCR4 was expressed with a high intensity in almost all of the 30 SCLC samples. In contrast, it was detected infrequently and with low intensity in the typical carcinoid and atypical carcinoid samples. There was a significant correlation between the immunohistochemistry and qRT-PCR data. Additionally, there was a significant negative relationship between CXCR4 expression and overall survival.
Conclusions: With increasing malignancy, BP-NEN clearly differ in the extent of CXCR4 expression. As in other tumor entities, CXCR4 overexpression significantly correlates with negative patient outcome. Due to its particular high expression rate in SCLC, CXCR4 may serve as a promising new target for diagnostic and pharmacological intervention as well as for peptide receptor-based radionuclide therapy.
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