Expression of CC chemokine receptor 7 in tonsillar cancer predicts cervical nodal metastasis, systemic relapse and survival

Abstract

The aim of this study was to evaluate the expression of CC chemokine receptor 7 (CCR7) in squamous cell cancer of the tonsil with respect to patterns of spread, relapse-free, overall and disease-specific survival. Eighty-four patients with squamous cell cancer of the tonsil were identified. There was a male predominance of 3 : 1 and the median age at diagnosis was 53 (range 35 -86) years. The median duration of follow-up was 33 (range 2 -124) months. There was a significant association between CCR7 immunopositivity and synchronous cervical nodal metastasis in patients with tonsillar cancer (Spearman's correlation coefficient 0.564; Po0.001). Relapse-free (P ¼ 0.0175), overall (P ¼ 0.0136) and disease-specific (P ¼ 0.0062) survival rates were significantly lower in patients whose tumours expressed high levels of CCR7. On multivariate analysis, high-level CCR7 staining predicted relapse-free (hazard ratio 3.0, 95% confidence intervals 1.1 -8.0, P ¼ 0.026) and disease-specific (hazard ratio 10.2, 95% confidence intervals 2.1 -48.6, P ¼ 0.004) survival. Fifteen percent of patients with the highest level of tumour CCR7 immunopositivity relapsed with systemic metastases. These data demonstrated that CCR7 expression was associated with cervical nodal and systemic metastases from tonsillar cancers. High levels of CCR7 expression predicted a poor prognosis.

Chemokine Receptors as Targets for Cancer Therapy

“…Overexpression of CCR7 in B16 melanoma cells has been shown to not only result in increased LN metastasis [38] but also contribute directly to melanoma cell tumorigenesis [39]. As with CXCR4 expression [40], CCR7 expression by human cancers has been correlated with poor patient outcome, which is consistent with a large array of data that links nodal metastasis with poor patient survival in most cancers, including melanoma [13,41,42]. Some breast cancer cell lines were reported to have elevated CXCR3, which also increased the incidence of lung metastasis [15].…”

Regulatory T cells and breast cancer: implications for immunopathogenesis

“…Furthermore, FoxP3 binds to the gene region upstream of the transcriptional start site of CCR7 and CXCR4 [97], two chemokine receptors recently reported to play an important role in cancer invasion and metastasis [98,99]. Thus, FoxP3 expressed in breast cancer cells might influence metastasis development by modulating the expression of these chemokine receptors or of other genes encoding cell surface or secreted molecules that alter tumor cell response to the environment [80].…”

Novel therapeutic approaches to squamous cell carcinoma of the head and neck using biologically targeted agents

“…In a recent study, a strong association was reported between CCR7 expression and synchronous nodal metastasis in patients with tonsillar cancer. [80] Only 1 of 11 (9.1%) patients with a negative CCR7 immunohistochemistry had nodal involvement at presentation, in contrast to 8 of 13 (61.5%) patients with "+" staining, 24 of 27 (88.9%) patients with "++" staining, and 29 of 33 (87.8%) patients with "+++" staining. Similarly, the degree of CCR7 immunopositivity was directly correlated with the extent of nodal metastasis at diagnosis, such that 43 of 44 (97.7%) patients with N2 or N3 disease had "++" or "+++" immunostaining at diagnosis.…”