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High CXCR4 expression in adenoid cystic carcinoma of the head and neck is associated with increased risk of locoregional recurrence
  1. Thomas J W Klein Nulent1,2,
  2. Robert J J van Es1,2,
  3. Matthijs H Valstar3,4,
  4. Ludwig E Smeele3,4,
  5. Laura A Smit5,
  6. Raquel Klein Gunnewiek6,
  7. Nicolaas P A Zuithoff7,
  8. Bart de Keizer8,
  9. Remco de Bree1,
  10. Stefan M Willems6
  1. 1Head and Neck Surgical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
  2. 2Oral and Maxillofacial Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
  3. 3Head and Neck Oncology and Surgery, Netherlands Cancer Institute/Antoni van Leeuwenhoek, Amsterdam, The Netherlands
  4. 4Oral and Maxillofacial Surgery, Amsterdam UMC Cancer Center and Academic Centre for Dentistry Amsterdam (ACTA), Amsterdam, The Netherlands
  5. 5Pathology, Netherlands Cancer Institute/Antoni van Leeuwenhoek, Amsterdam, The Netherlands
  6. 6Pathology, University Medical Center Utrecht, Utrecht, The Netherlands
  7. 7Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
  8. 8Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands
  1. Correspondence to Dr Thomas J W Klein Nulent, Department of Head and Neck Surgical Oncology, University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands; t.j.w.kleinnulent{at}


Aim Treatment options for head and neck adenoid cystic carcinoma (AdCC) are limited in advanced disease. Chemokine receptor type 4 (CXCR4) is present in various tumour types, including AdCC. Upregulation is associated with tumour recurrence and metastasis. New CXCR4-specific diagnostic and therapeutic target agents have recently been available. This study aimed to analyse CXCR4 expression in a cohort of primary head and neck AdCC.

Methods After histopathological revision, tumour tissues of 73 consecutive patients with AdCC over 1990–2016 were sampled on a tissue microarray. Slides were immunohistochemically stained for CXCR4 and semiquantitatively scored. Associations between protein expression and cliniopathological parameters were tested. HRs were calculated using a Cox proportional hazard model.

Results Sixty-six tumours could be analysed. CXCR4 expression was present in 81% of the tumours with a median of 29% (IQR 1–70) positive cells. Expression was univariately correlated to perineural growth (Spearman ρ .26, p=0.04) and bone invasion (Spearman ρ .32, p=0.01), but not with tumour grade.

CXCR4 expression in the primary tumour was significantly higher in tumours that recurred as compared with those that did not recur (median 60%, IQR 33–72 vs 12%, IQR 1–70, Kruskal-Wallis p=0.01). After dichotomisation, >25% of CXCR4 expressions proved an independent prognosticator for a reduced recurrence-free survival (RFS) (HR 7.2, 95% CI 1.5 to 72.4, p=0.04).

Conclusion CXCR4 is expressed in the majority of primary AdCCs and independently correlated to worse RFS, suggesting CXCR4 as a target for imaging and therapy purposes in patients with advanced AdCC.

  • immunohistochemistry
  • carcinoma
  • salivary gland tumours
  • surgical pathology
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  • Handling editor Dhirendra Govender.

  • Correction notice This article has been corrected since it apeared Online First. Author Stefan Willems has been corrected to Stefan M Willems. Table 1 layout has been adjusted slightly.

  • Contributors All authors included on this paper fulfil the criteria of authorship. There is no one else who fulfils the criteria who has been excluded as an author.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The research protocol was approved by the University Medical Center Utrecht Medical Research Ethics Committee and Biobank Research Ethics Committee (protocol numbers 16–564 and 17–073, respectively).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.

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