Expression patterns of Bmi-1 and p16 significantly correlate with overall, disease-specific, and recurrence-free survival in oropharyngeal squamous cell carcinoma

BACKGROUND: The objective of this study was to link expression patterns of B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) and p16 to patient outcome (recurrence and survival) in a cohort of 252 patients with oral and oropharyngeal squamous cell cancer (OSCC). METHODS: Expression levels of Bmi-1 and p16 in samples from 252 patients with OSCC were evaluated immunohistochemically using the tissue microarray method. Staining intensity was determined by calculating an intensity reactivity score (IRS). Staining intensity and the localization of expression within tumor cells (nuclear or cytoplasmic) were correlated with overall, disease-specific, and recurrence-free survival. RESULTS: The majority of cancers were localized in the oropharynx (61.1%). In univariate analysis, patients who had OSCC and strong Bmi-1 expression (IRS >10) had worse outcomes compared with patients who had low and moderate Bmi-1 expression (P = .008; hazard ratio [HR], 1.82; 95% confidence interval [CI], 1.167-2.838); this correlation was also observed for atypical cytoplasmic Bmi-1 expression (P = .001; HR, 2.164; 95% CI, 1.389-3.371) and for negative p16 expression (P < .001; HR, 0.292; 95% CI, 0.178-0.477). The combination of both markers, as anticipated, had an even stronger correlation with overall survival (P < .001; HR, 8.485; 95% CI, 4.237-16.994). Multivariate analysis demonstrated significant results for patients with oropharyngeal cancers, but not for patients with oral cavity tumors: Tumor classification (P = .011; HR, 1.838; 95%CI, 1.146-2.947) and the combined marker expression patterns (P < .001; HR, 6.254; 95% CI, 2.869-13.635) were correlated with overall survival, disease-specific survival (tumor classification: P = .002; HR, 2.807; 95% CI, 1.477-5.334; combined markers: P = .002; HR, 5.386; 95% CI, 1.850-15.679), and the combined markers also were correlated with recurrence-free survival (P = .001; HR, 8.943; 95% CI, 2.562-31.220). CONCLUSIONS: Cytoplasmic Bmi-1 expression, an absence of p16 expression, and especially the combination of those 2 predictive markers were correlated negatively with disease-specific and recurrence-free survival in patients with oropharyngeal cancer. Therefore, the current results indicate that these may be applicable as predictive markers in combination with other factors to select patients for more aggressive treatment and follow-up. Cancer 2011;. © 2011 American Cancer Society

Initial Job Choice in the Greater China Region: The role of corporate social responsibility

Job application choice is influenced by job/organisational attributes, both traditional ones, such as salary, prospects, location, company type and newer ones, such as corporate social responsibility (CSR). To examine the varying importance of these and the impacts of location and gender for initial job applications, potential job applicants were surveyed who were about to join the jobs market based in China, Hong Kong and Taiwan, often grouped together as the Greater China region. Using conjoint analysis of different job scenarios it is found that the importance of different job characteristics does vary across the region, although with no clear result regarding gender. The theoretical and practical implications of this work is discussed

NF-κB is Required for Survival of Immature Auditory Hair Cells In Vitro

Damage to auditory hair cells in the inner ear as a consequence of aging, disease, acoustic trauma, or exposure to ototoxins underlies most cases of hearing impairment. Because the mammalian ear cannot replace damaged hair cells, loss of hearing is irreversible and progressive throughout life. One of the current goals of inner ear biology is to develop therapeutic strategies to prevent hair cell degeneration. Although important progress has been made in discovering factors that mediate hair cell death, very little is known about the molecular pathway(s) that signal survival. Here we considered the role of NF-κB, a ubiquitous transcription factor that plays a major role in the regulation of many apoptosis- and stress-related genes, in mediating hair cell survival. NF-κB was detected in a constitutively active form in the organ of Corti of 5-day-old rats. Selective inhibition of NF-κB through use of a cell-permeable inhibitory peptide in vitro caused massive degeneration of hair cells within 24 h of inhibitor application. Hair cell death occurred through an apoptotic pathway through activation of caspase-3 and may involve transcriptional down-regulation of the gadd45β gene, an anti-apoptotic NF-κB target. In view of our results, it seems likely that NF-κB may participate in normal hair cell function