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. 2017 Jul 14:5:28-36.
doi: 10.1016/j.ctro.2017.06.004. eCollection 2017 Aug.

SDF-1/CXCR4 expression in head and neck cancer and outcome after postoperative radiochemotherapy

Chiara De-Colle  1 , David Mönnich  1   2 , Stefan Welz  1 , Simon Boeke  1 , Bence Sipos  3 , Falko Fend  3 , Paul-Stefan Mauz  4 , Inge Tinhofer  5   6 , Volker Budach  5   6 , Jehad Abu Jawad  7   8 , Martin Stuschke  7   8 , Panagiotis Balermpas  9   10 , Claus Rödel  9   10 , Anca-Ligia Grosu  11   12 , Amir Abdollahi  13   14   15   16   17 , Jürgen Debus  13   14   15   16   18 , Christine Bayer  19 , Claus Belka  19   20 , Steffi Pigorsch  19   21 , Stephanie E Combs  19   21 , Fabian Lohaus  22   23   24   25 , Annett Linge  22   23   24   25 , Mechthild Krause  22   23   24   25   26 , Michael Baumann  22   23   24   25   26   27 , Daniel Zips  1   2 , Apostolos Menegakis  1
Affiliations

SDF-1/CXCR4 expression in head and neck cancer and outcome after postoperative radiochemotherapy

Chiara De-Colle et al. Clin Transl Radiat Oncol. .

Abstract

Introduction: Outcome after postoperative radiochemotherapy (RT-CT) for patients with advanced head and neck squamous cell carcinomas (HNSCC) remains unsatisfactory, especially among those with HPV negative tumours. Therefore, new biomarkers are needed to further define subgroups for individualised therapeutic approaches. Preclinical and first clinical observations showed that the chemokine receptor CXCR4 and its ligand SDF-1 (CXCL12) play an important role in tumour cell proliferation, survival, cancer progression, metastasis and treatment resistance. However, the data on the prognostic value of SDF-1/CXCR4 expression for HNSCC are conflicting. The aim of our hypothesis-generating study was to retrospectively explore the prognostic potential of SDF-1/CXCR4 in a well-defined cohort of HNSCC patients collected within the multicenter biomarker study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG).

Material and methods: Patients with stage III and IVA HNSCC of the oral cavity, oropharynx and hypopharynx were treated with resection and adjuvant radiotherapy (RT) with ≥60 Gy and concurrent cisplatin-based chemotherapy (CT). Tissue micro-arrays (TMAs) from a total of 221 patients were generated from surgical specimens, 201 evaluated for the SDF-1 and CXCR4 expression by immunofluorescence and correlated with clinico-pathological and outcome data.

Results: In univariate and multivariate analyses intracellular SDF-1 expression was associated with lower loco-regional control (LRC) in the entire patient group as well as in the HPV16 DNA negative subgroup. CXCR4 expression showed a trend for lower LRC in the univariate analysis which was not confirmed in the multivariate analysis. Neither for SDF-1 nor CXCR4 expression associations with distant metastasis free or overall survival were found.

Conclusions: Our exploratory data support the hypothesis that overexpression of intracellular SDF-1 is an independent negative prognostic biomarker for LRC after postoperative RT-CT in high-risk HNSCC. Prospective validation is warranted and further exploration of SDF-1/CXCR4 as a potential therapeutic target to overcome treatment resistance in HNSCC appears promising.

Keywords: Biomarker; CXCR4; Head and neck cancer; Postoperative radiochemotherapy; Prognostic; SDF-1.

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Figures

Fig. 1
Fig. 1
Representative images of SDF-1 immunofluorescent stained tumour sections. (A) Membrane staining (score 3). (B) Intracellular staining (score 2). (C) Negative staining (score 0). SDF-1 is shown in green, DAPI in blue. Similar staining patterns and intensities were observed for CXCR4. Original image magnification: 400×.
Fig. 2
Fig. 2
A–D: Kaplan-Meier curves for locoregional tumour control in all patients (A and C) and patients with HPV16 DNA negative tumours only (B and D) according to the SDF-1 and CXCR4 intracellular expression.
See this image and copyright information in PMC

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