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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. 1 Head and Neck Surgical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
  2. 2 Oral and Maxillofacial Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
  3. 3 Head and Neck Oncology and Surgery, Netherlands Cancer Institute/Antoni van Leeuwenhoek, Amsterdam, The Netherlands
  4. 4 Oral and Maxillofacial Surgery, Amsterdam UMC Cancer Center and Academic Centre for Dentistry Amsterdam (ACTA), Amsterdam, The Netherlands
  5. 5 Pathology, Netherlands Cancer Institute/Antoni van Leeuwenhoek, Amsterdam, The Netherlands
  6. 6 Pathology, University Medical Center Utrecht, Utrecht, The Netherlands
  7. 7 Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
  8. 8 Radiology 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}umcutrecht.nl

Abstract

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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Footnotes

  • 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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