Syk, a non-receptor tyrosine kinase, is an important component of immunoreceptor signaling in hematopoietic cells. It has been implicated in key regulatory pathways including phosphoinositide 3-kinase and phospholipase C; (PLC;) activation in B cells and integrin signaling in platelets and bronchial epithelial cells. Recently, potential roles in cancer have been reported. In breast cancers, reduced Syk expression was associated with invasion, and its overexpression in cell lines was shown to inhibit cell motility. In contrast, Syk has been shown to mediate chemomigration in nasopharyngeal carcinoma cells. Its role in squamous cell carcinomas of the head and neck (SCCHN) has not yet been investigated. Syk mRNA and protein expression was detected in 6 of 10 SCCHN cell lines. When Syk was transfected into Syknegative cells (SIHN-011A), chemomigration was enhanced in vitro and this was associated with activation of PLC;1. Conversely, abrogation of Syk activity by pharmacologic inhibition or small interfering RNA in HN6 cells with high levels of endogenous expression inhibited migration, haptotaxis, and engagement with matrix proteins; this was accompanied by decreased levels of phosphorylated AKT. Similar effects were seen in Syk-positive CAL 27 cells but not in Syk-negative SIHN-011A cells. Immunoprecipitation suggested co-association of Syk with epidermal growth factor receptor and GRB-2. Syk expression in SCCHN patient tissues was examined by semiquantitative real-time PCR (n = 45) and immunohistochemistry (n = 38) in two independent cohorts. Higher levels of Syk expression were observed in tumors and lymph node metastases relative to normal tissues. High Syk expression significantly correlated with worse survival and may be of prognostic value in SCCHN due to its potential role in cell migration and invasion. [Cancer Res 2007;67(16):7907-16]

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.

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An 84-year-old man presented with a 2-month history of intermittent stridor and worsening difficulty in breathing. Chest X-ray and flexible nasendoscopy were unremarkable but following further deterioration a CT scan revealed an obstructing lesion in the distal trachea. Bronchoscopy revealed an infiltrative tumour arising 3 cm above the carina causing 90% obstruction. The mass was biopsied and surgically debrided to leave a patent airway. Histological analysis revealed a diagnosis of adenoid cystic carcinoma. Transthoracic surgical resection was unsuccessful and the patient continues to be effectively managed with periodic bronchoscopic debulking and radiotherapy. This case highlights the diagnostic and therapeutic dilemmas posed by distal tracheal lesions and the need for specialist input for effective management.