ABSTRACT
BACKGROUND: Recently, the management of head and neck squamous cell carcinoma (HNSCC) has focused considerable attention on biomarkers, which may influence outcomes. Tests for human papilloma infection, including direct assessment of the virus as well as an associated tumour suppressor gene p16, are considered reproducible. Tumours from familial melanoma syndromes have suggested that nuclear localisation of p16 might have a further role in risk stratification. We hypothesised p16 staining that considered nuclear localisation might be informative for predicting outcomes in a broader set of HNSCC tumours not limited to the oropharynx, human papilloma virus (HPV) status or by smoking status. METHODS: Patients treated for HNSCC from 2002 to 2006 at UNC (University of North Carolina at Chapel Hill) hospitals that had banked tissue available were eligible for this study. Tissue microarrays (TMA) were generated in triplicate. Immunohistochemical (IHC) staining for p16 was performed and scored separately for nuclear and cytoplasmic staining. Human papilloma virus staining was also carried out using monoclonal antibody E6H4. p16 expression, HPV status and other clinical features were correlated with progression-free (PFS) and overall survival (OS). RESULTS: A total of 135 patients had sufficient sample for this analysis. Median age at diagnosis was 57 years (range 20-82), with 68.9% males, 8.9% never smokers and 32.6% never drinkers. Three-year OS rate and PFS rate was 63.0% and 54.1%, respectively. Based on the p16 staining score, patients were divided into three groups: high nuclear, high cytoplasmic staining group (HN), low nuclear, low cytoplasmic staining group (LS) and high cytoplasmic, low nuclear staining group (HC). The HN and the LS groups had significantly better OS than the HC group with hazard ratios of 0.10 and 0.37, respectively, after controlling for other factors, including HPV status. These two groups also had significantly better PFS than the HC staining group. This finding was consistent for sites outside the oropharynx and did not require adjustment for smoking status. CONCLUSION: Different p16 protein localisation suggested different survival outcomes in a manner that does not require limiting the biomarker to the oropharynx and does not require assessment of smoking status.
Subject(s)
Carcinoma, Squamous Cell/metabolism , Cyclin-Dependent Kinase Inhibitor p16/metabolism , Head and Neck Neoplasms/metabolism , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/genetics , Case-Control Studies , Cell Nucleus/genetics , Cell Nucleus/metabolism , Cohort Studies , Cyclin-Dependent Kinase Inhibitor p16/genetics , Disease-Free Survival , Female , Genes, Tumor Suppressor , Head and Neck Neoplasms/genetics , Humans , Male , Middle Aged , Papillomaviridae/genetics , Papillomaviridae/metabolism , Papillomavirus Infections/genetics , Papillomavirus Infections/metabolism , Squamous Cell Carcinoma of Head and Neck , Survival Rate , Young AdultSubject(s)
Adenocarcinoma/pathology , Brain Neoplasms/secondary , Lung Neoplasms/pathology , Neoplasm Recurrence, Local/pathology , Adenocarcinoma/surgery , Adenocarcinoma/therapy , Adenocarcinoma of Lung , Adult , Aged , Aged, 80 and over , Brain Neoplasms/therapy , Clinical Trials, Phase I as Topic , Disease Progression , Female , Humans , Lung Neoplasms/surgery , Lung Neoplasms/therapy , Magnetic Resonance Imaging/methods , Male , Middle Aged , Neoplasm StagingABSTRACT
In this study on the effects of attributions of responsibility for traumatic events, stress, coping, and symptoms of posttraumatic stress disorder (PTSD) were measured, including intrusive thoughts among 130 victims of serious motor vehicle accidents (MVAs) 14-21 days and 3, 6, and 12 months after their accident. MVA victims and 43 control participants were categorized by accident and attribution of responsibility for their accidents (self-responsible, other-responsible, and control). Although initially all MVA victims reported higher levels of intrusive thoughts and were more likely to meet criteria for PTSD diagnoses, only other-responsible participants continued to demonstrate increased distress 6 and 12 months postaccident. Self-responsible participants used more self-blame coping than other-responsible participants, although within the self-responsible group, use of self-blame was associated with more distress.
