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. 2015 Feb 20;6(5):3346-58.
doi: 10.18632/oncotarget.3242.

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

Daniel Kaemmerer  1 , Christiane Reimann  2 , Elisa Specht  2 , Ralph M Wirtz  3 , Manal Sayeg  4 , Richard P Baum  5 , Stefan Schulz  2 , Amelie Lupp  2
Affiliations

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

Daniel Kaemmerer et al. Oncotarget. .

Abstract

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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Conflict of interest statement

Conflict of Interests

Kaemmerer D. received support for travelling to meetings by the companies Pfizer and Ipsen. All other authors declare no conflict of interests.

Figures

Figure 1
Figure 1
Overall survival among patients with TC, ATC, and SCLC.
Figure 2
Figure 2
Kaplan-Meier curve of overall patient survival for TC, ATC, and SCLC.
Figure 3
Figure 3
A) IRS (0–12) of CXCR4 immunohistochemistry. B) CXCR4 mRNA levels (ΔCT values).
Figure 4
Figure 4
A) Kaplan-Meier survival curves for negative-tomild (IRS 0–4) and moderate-to-strong (IRS 5–12) CXCR4 expression as determined by immunohistochemistry. B) Kaplan-Meier curve of CXCR4 mRNA levels (0–3).
Figure 5
Figure 5. CXCR4 expression in the tumor samples of 3 patients with TC (1-3), of 3 patients with ATC (4-6), and 3 patients with SCLC (7-9), (immunohistochemistry; original magnification: 400x)
Figure 6
Figure 6
68Ga-CPCR4-2 PET/CT (transversal images): local recurrence of an centrally localized SCLC (upper panel: PET scan, middle panel: CT scan, lower panel: PET + CT fusion image).
See this image and copyright information in PMC

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