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

T.J.W. Klein Nulent, R.J.J. van Es, M.H. Valstar, L.E. Smeele, L.A. Smit, Raquel Klein Gunnewiek, N.P.A. Zuithoff, B. de Keizer, R. de Bree, S.M. Willems

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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.

Original languageEnglish
Pages (from-to)476-482
Number of pages7
JournalJournal of clinical pathology
Issue number8
Publication statusPublished - 1 Aug 2020


  • carcinoma
  • immunohistochemistry
  • salivary gland tumours
  • surgical pathology

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