Research Papers:

Primary tumor-associated expression of CXCR4 predicts formation of local and systemic recurrency in head and neck squamous cell carcinoma

Andreas Knopf _, Leila Bahadori, Kristin Fritsche, Guido Piontek, Cord-Christian Becker, Percy Knolle, Achim Krüger, Henning Bier and Yin Li

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Oncotarget. 2017; 8:112739-112747. https://doi.org/10.18632/oncotarget.22562

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Andreas Knopf1, Leila Bahadori1, Kristin Fritsche1, Guido Piontek1, Cord-Christian Becker1, Percy Knolle2, Achim Krüger2, Henning Bier1 and Yin Li1

1Otorhinolaryngology, Head and Neck Surgery, Institute of Molecular Immunology & Experimental Oncology, 81675 München, Germany

2Institute of Molecular Immunology & Experimental Oncology, 81675 München, Germany

Correspondence to:

Andreas Knopf, email: [email protected]

Keywords: CXCR4; CXCL12; head and neck squamous cell carcinoma; recurrency; metastasis

Received: June 23, 2017    Accepted: September 30, 2017    Published: November 20, 2017


Objectives: Despite modern treatment regimens, overall survival in head and neck squamous cell carcinomas (HNSCC) is less than 50% due to local and systemic disease recurrency. The current study aims to identify molecular markers in primary tumor specimens that predict the risk for local and systemic recurrency at the time of initial diagnosis.

Methods: The study included clinic-pathological data of 1,057 HNSCC. MMP2/9, TIMP1/2, CXCR4, and CXCL12 immunohistochemistry was done in 150 randomly selected specimens. For statistics, we employed Chi square, Fisher exact, and Student’s t-test. Overall survival (OS) was calculated by Kaplan–Meier and log-rank test. Prognostic variables were subsequently evaluated by Cox regression for forward selection.

Results: CXCR4 positive specimens demonstrated a significant increased risk for tumor recurrency associated death (rT: HR 10.07; p=0.001 / rN: HR 5.04; p=0.013 / rM: HR 2.49; p=0.029) when compared with their unaltered counterparts. Expression of MMP9, TIMP2, CXCR4, and CXCL12 was significantly increased in distant metastasized patients (p<0.0001) and showed significant cross-correlation. In addition, CXCR4 positivity was associated with an increased risk to die due to enhanced T or N status (T1/2 vs. T3/4: HR 5.78; p=0.017; N0 vs. N+: HR 5.18; p=0.033).

Conclusion: CXCR4 positivity in tumor samples at initial diagnosis were associated with reduced overall survival, in particular with respect to increasing T/N status, local and systemic recurrency.

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