Differential expression and prognostic value of the chemokine receptor CXCR4 in bronchopulmonary neuroendocrine neoplasms.

Daniel Kaemmerer,Manal Sayeg,Richard P Baum,Stefan Schulz,Elisa Specht,Amelie Lupp,Christiane Reimann,Ralph M Wirtz

doi:10.18632/oncotarget.3242

Daniel Kaemmerer, Manal Sayeg + Show 6 more

Open Access

https://doi.org/10.18632/oncotarget.3242

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Journal: Oncotarget	Publication Date: Dec 30, 2014
Citations: 79	License type: cc-by

Affiliation: Zentralklinik Bad Berka, Jena University Hospital

Abstract

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. 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. 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. 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.

Highlights

For many tumors, the overexpression of the chemokine receptor CXCR4 is associated with increased malignancy and poor patient outcomes
Neuroendocrine neoplasms (NEN) can be found in many organs and represent a heterogeneous group of malignancies deriving from the neuroendocrine system
Within the tumor entity subgroups, no significant association between CXCR4 expression and OS was found

Summary

Introduction

The overexpression of the chemokine receptor CXCR4 is associated with increased malignancy and poor patient outcomes. Comprehensive data for neuroendocrine neoplasms of the lung are still lacking. Neuroendocrine neoplasms (NEN) can be found in many organs and represent a heterogeneous group of malignancies deriving from the neuroendocrine system. NEN are commonly classified into functioning and non-functioning tumors, depending on the hormone secretion[2]. One quarter of all NEN are located in the lung. The growing importance of bronchopulmonary neuroendocrine neoplasms (BP-NEN) is further underlined by a distinct increase in the incidence of BP-NEN in recent years[3]. Typical carcinoids (TC) and atypical carcinoids (ATC) are well-differentiated neuroendocrine tumors of the lung. Small cell lung cancers (SCLC) and large cell neuroendocrine carcinomas (LCNEC) are undifferentiated[4]

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