Strahlentherapie und Onkologie

, Volume 192, Issue 1, pp 47–54 | Cite as

Prognostic value of CXCL12 and CXCR4 in inoperable head and neck squamous cell carcinoma

  • Margret Rave-Fränk
  • Narges Tehrany
  • Julia Kitz
  • Martin Leu
  • Hanne Elisabeth Weber
  • Peter Burfeind
  • Henning Schliephake
  • Martin Canis
  • Tim Beissbarth
  • Holger Michael Reichardt
  • Hendrik Andreas WolffEmail author
Original Article



The chemokine CXCL12 and its receptor CXCR4 can affect tumor growth, recurrence, and metastasis. We tested the hypothesis that the CXCL12 and CXCR4 expression influences the prognosis of patients with inoperable head and neck cancer treated with definite radiotherapy or chemoradiotherapy.


Formalin-fixed paraffin-embedded pretreatment tumor tissue from 233 patients with known HPV/p16INK4A status was analyzed. CXCL12 and CXCR4 expressions were correlated with pretreatment parameters and survival data by univariate and multivariate Cox regression.


CXCL12 was expressed in 43.3 % and CXCR4 in 66.1 % of the samples and both were correlated with HPV/p16INK4A positivity. A high CXCL12 expression was associated with increased overall survival (p = 0.036), while a high CXCR4 expression was associated with decreased metastasis-free survival (p = 0.034).


A high CXCR4 expression could be regarded as a negative prognostic factor in head and neck cancer because it may foster metastatic spread. This may recommend CXCR4 as therapeutic target for combating head and neck cancer metastasis.


Head and neck cancer Squamous cell cancer Chemokines Radio(chemo)therapy Prognosis 

Prognostischer Stellenwert von CXCL12 und CXCR4 bei inoperablen Kopf-Hals-Tumoren



Das Chemokin CXCL12 und sein Rezeptor CXCR4 beeinflussen Tumorwachstum, Auftreten von Rezidiven und Metastasierung. Es wurde die Hypothese geprüft, dass ein Zusammenhang der CXCL12- und CXCR4-Expression mit der Prognose von Patienten bestehe, die wegen eines inoperablen Kopf-Hals-Tumors eine primäre Radio- oder Radiochemotherapie erhielten. Dabei wurde auch der HPV-Status der Patienten berücksichtigt.


Formalinfixierte Proben aus unbehandelten Tumoren von 233 Patienten mit bekanntem HPV/p16INK4A-Status wurden ausgewertet. Die CXCL12- und CXCR4-Expression wurde mit klinischen Parametern und Überlebensdaten mittels uni- und multivariater Cox Regression analysiert.


CXCL12 wurde von 43,3 %, CXCR4 von 66,1 % der Tumoren exprimiert, und beide Marker korrelierten mit einer HPV/p16INK4A-Expression. Eine hohe CXCL12-Expression war mit einem verbesserten Gesamtüberleben (p = 0,036), eine hohe CXCR4-Expression mit einem reduzierten fernmetastasenfreien Überleben (p = 0,034) assoziiert.


Eine hohe CXCR4-Expression erscheint auch für Patienten mit inoperablen Kopf-Hals-Tumoren als negativer prognostischer Faktor, weil es Metastasierungsprozesse fördert. Eine gezielte Unterdrückung der CXCL12-/CXCR4-Signalwege kann eine Möglichkeit zur Reduktion der Metastasierung sein.


Kopf-Hals-Plattenepithelkarzinom Plattenepithelkarzinome Chemokin Radio(chemo)therapie Prognose 


Compliance with ethical guidelines

Conflict of interest

M. Rave-Fränk, N. Tehrany, J. Kitz, M. Leu, H.E. Weber, P. Burfeind, H. Schliephake, M. Canis, T. Beissbarth, H.M. Reichardt, and H.A. Wolff state that there are no conflicts of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Margret Rave-Fränk
    • 1
  • Narges Tehrany
    • 1
  • Julia Kitz
    • 2
  • Martin Leu
    • 1
  • Hanne Elisabeth Weber
    • 1
  • Peter Burfeind
    • 3
  • Henning Schliephake
    • 4
  • Martin Canis
    • 5
  • Tim Beissbarth
    • 6
  • Holger Michael Reichardt
    • 7
  • Hendrik Andreas Wolff
    • 1
    Email author
  1. 1.Department of Radiotherapy and Radiation OncologyUniversity Medical Center GöttingenGöttingenGermany
  2. 2.Department of PathologyUniversity Medical Center GöttingenGöttingenGermany
  3. 3.Department of Human GeneticsUniversity Medical Center GöttingenGöttingenGermany
  4. 4.Department of Oral and Maxillofacial SurgeryUniversity Medical Center GöttingenGöttingenGermany
  5. 5.Department of Otorhinolaryngology, Head and Neck SurgeryUniversity Medical Center GöttingenGöttingenGermany
  6. 6.Institute of Medical StatisticsUniversity Medical Center GöttingenGöttingenGermany
  7. 7.Institute for Cellular and Molecular ImmunologyUniversity Medical Center GöttingenGöttingenGermany

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