High CXCR4 expression in adenoid cystic carcinoma of the head and neck is associated with increased risk of locoregional recurrence

Thomas J W Klein Nulent*, Robert J J van Es, Matthijs H Valstar, Ludwig E Smeele, Laura A Smit, Raquel Klein Gunnewiek, Nicolaas P A Zuithoff, Bart de Keizer, Remco de Bree, Stefan M Willems

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)


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 rho .26, p=0.04) and bone invasion (Spearman rho .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.

Original languageEnglish
Pages (from-to)476-482
Number of pages7
JournalJournal of Clinical Pathology
Issue number8
Early online date16-Jan-2020
Publication statusPublished - Aug-2020
Externally publishedYes


  • immunohistochemistry
  • carcinoma
  • salivary gland tumours
  • surgical pathology

Cite this