TY - JOUR
T1 - High CXCR4 expression in adenoid cystic carcinoma of the head and neck is associated with increased risk of locoregional recurrence
AU - Klein Nulent, T.J.W.
AU - van Es, R.J.J.
AU - Valstar, M.H.
AU - Smeele, L.E.
AU - Smit, L.A.
AU - Klein Gunnewiek, Raquel
AU - Zuithoff, N.P.A.
AU - de Keizer, B.
AU - de Bree, R.
AU - Willems, S.M.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - 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.
AB - 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.
KW - carcinoma
KW - immunohistochemistry
KW - salivary gland tumours
KW - surgical pathology
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85077979854&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31948995
UR - http://www.scopus.com/inward/record.url?scp=85077979854&partnerID=8YFLogxK
U2 - https://doi.org/10.1136/jclinpath-2019-206273
DO - https://doi.org/10.1136/jclinpath-2019-206273
M3 - Article
C2 - 31948995
SN - 0021-9746
VL - 73
SP - 476
EP - 482
JO - Journal of clinical pathology
JF - Journal of clinical pathology
IS - 8
ER -