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The putative tumor suppressor protein spinophilin has been recently involved in the pathogenesis of lung, liver, and other types of cancer. Previous studies also indicate that a loss of spinophilin in combination with functional impairment of p53 drives tumor progression. To date, no data exist about the role of spinophilin in head and neck squamous cell carcinoma (HNSCC). In the present study, we evaluated spinophilin and p53 expression by immunohistochemistry in 85 patients with nonmetastatic HNSCC. Kaplan-Meier curves and multivariate Cox proportional models were used to define the prognostic relevance of spinophilin for patients with HNSCC. Overall, immunoreactivity for spinophilin was reduced in 40 tumors (47%). Nine cases (10.5%) showed complete loss of spinophilin. Kaplan-Meier curve analysis demonstrated that reduced spinophilin expression is associated with poor overall survival (P = .022). Concomitant analysis of spinophilin and p53 further showed that patients with reduced spinophilin expression and nuclear p53 staining have a significantly decreased overall survival (hazard ratio, 1.96; 95% confidence interval, 1.06-3.61; P = .030). In conclusion, the combination of reduced spinophilin expression and nuclear p53 staining indicates a poor prognosis in HNSCC patients. Based on our results, spinophilin might play a previously unrecognized role in the pathogenesis of HNSCC., (© 2014.)

Purpose: Radiochemotherapy of head and neck cancer causes severe mucositis in most patients. We investigated whether palifermin reduces this debilitating sequela., Methods: We conducted a multicenter, double-blind, randomized, placebo-controlled trial in 186 patients with stages II to IVB carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx. Patients received 60 or 66 Gy after complete (R0) or incomplete resection (R1), respectively, at 2 Gy/fraction and five fractions per week. Cisplatin 100 mg/m(2) was administered on days 1 and 22 (and on day 43 with R1). Patients were randomly assigned to receive weekly palifermin 120 μg/kg or placebo from 3 days before and continuing throughout radiochemotherapy. Trained evaluators performed oral assessments twice weekly. The primary end point was the incidence of severe oral mucositis (WHO grades 3 to 4). Overall survival and time to locoregional progression were also assessed. Analysis was by intention to treat., Results: Severe oral mucositis was seen in 47 (51%) of 92 patients administered palifermin and 63 (67%) of 94 administered placebo (P = .027). Palifermin decreased the duration (median, 4.5 v 22.0 days) and prolonged the time to develop (median, 45 v 32 days) severe mucositis. Neither patient-reported mouth and throat soreness scores nor treatment breaks differed between treatment arms. After median follow-up of 32.8 months, 23 deaths (25%) had occurred in both treatment arms, and disease had recurred in 25 (27%) and 22 (24%) of palifermin- and placebo-treated patients, respectively., Conclusion: Palifermin reduced the occurrence of severe oral mucositis in patients with head and neck cancer undergoing postoperative radiochemotherapy. Additional clinical exploration of palifermin with postoperative radiochemotherapy would be useful.