RESUMO
BACKGROUND: Recent genetic studies have implicated p53 mutation as a significant risk factor for therapeutic failure in squamous cell carcinoma of the head and neck (SCCHN). However, in a recent meta-analysis in the literature of p53 from major anatomical subsites (larynx, oral cavity, oropharynx/hypopharynx), associations between patient survival and p53 status were ambiguous. METHODS: The authors examined a cohort of SCCHNs using a previously developed biomarker combination that likely predicts p53 status based on p53/MDM2 expression levels determined by immunohistochemistry (IHC). In addition, the authors generated and validated an antibody to MTBP (an MDM2 binding protein that alters p53/MDM2 homeostasis and may contribute to metastatic suppression) and have incorporated data for MTBP expression into the current analyses. RESULTS: Analysis of expression data for p53 and MDM2 in 198 SCCHN patient samples revealed that the biomarker combination p53 + ve/MDM2-low (likely indicative of p53 mutation) was significantly associated with reduced overall survival (log-rank P = .035) and was an independent prognostic factor (P = .013; HR, 1.705; 95% CI, 1.12-2.60); thus, these data were compatible with earlier genetic analyses. By using IHC for p53 and MDM2 to dichotomize patients, the authors found that loss of MTBP expression was significantly associated with reduced survival (log-rank P = .004) and was an independent prognostic factor (P = .004; HR, 2.78; 95% CI, 1.39-5.54) in p53 + ve/MDM2-low patients. CONCLUSIONS: These results represent the first examination of MTBP expression in human tissues and provide evidence for a p53 status-dependent role for MTBP in suppressing disease progression in SCCHN patients as well as confirming a role for p53 pathway function in delaying disease progression.
Assuntos
Proteínas de Transporte/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Idoso , Biomarcadores Tumorais/metabolismo , Western Blotting , Carcinoma/genética , Carcinoma/metabolismo , Carcinoma/mortalidade , Carcinoma/patologia , Carcinoma de Células Escamosas , Proteínas de Transporte/genética , Progressão da Doença , Feminino , Imunofluorescência , Genes p53 , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Mutação , Neoplasias de Células Escamosas/genética , Neoplasias de Células Escamosas/metabolismo , Neoplasias de Células Escamosas/mortalidade , Neoplasias de Células Escamosas/patologia , Reação em Cadeia da Polimerase , Prognóstico , Proteínas Proto-Oncogênicas c-mdm2/genética , Fatores de Risco , Carcinoma de Células Escamosas de Cabeça e Pescoço , Análise Serial de Tecidos , Falha de TratamentoRESUMO
BACKGROUND: The contemporary treatment of oropharyngeal squamous cell carcinoma (SCC) is an area of debate. We report outcomes of a minimally invasive approach involving transoral laser microsurgery (TLM). METHODS: A consecutive series of patients (n = 153) undergoing primary TLM for oropharyngeal SCC from 2006 to 2013 was studied. Human papillomavirus (HPV) status was determined by p16 immunohistochemistry and high-risk HPV DNA in situ hybridization. Survival analyses were evaluated using Kaplan-Meier statistics. RESULTS: Tumor subsites included tonsil (n = 94; 61.5%), tongue base (n = 38; 24.8%), and soft palate (n = 21; 13.7%), with the majority being American Joint Committee on Cancer (AJCC) stage III/IVa (n = 124; 81.0%) and HPV-positive (n = 101; 66.0%). Three-year overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were 84.5%, 91.7%, and 78.2%, respectively. HPV-positivity portended favorable oncologic outcomes. One-year gastrostomy tube (G-tube) dependency was 1.3%. CONCLUSION: To the best of our knowledge, this is the largest single-center TLM oropharyngeal SCC series to date. Our data suggest that TLM +/- postoperative radiotherapy (PORT) results in at least as good oncologic outcomes as chemoradiotherapy (CRT), while conferring swallowing function advantages. © 2016 Wiley Periodicals, Inc. Head Neck , 2016 © 2016 Wiley Periodicals, Inc. Head Neck 38:1263-1270, 2016.
Assuntos
Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/cirurgia , Terapia a Laser/métodos , Microcirurgia/métodos , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/cirurgia , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia Adjuvante , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Estimativa de Kaplan-Meier , Terapia a Laser/mortalidade , Masculino , Microcirurgia/mortalidade , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Cirurgia Endoscópica por Orifício Natural/métodos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/fisiopatologia , Neoplasias Orofaríngeas/patologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/fisiopatologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Carcinoma de Células Escamosas de Cabeça e Pescoço , Análise de Sobrevida , Resultado do Tratamento , Reino UnidoRESUMO
OBJECTIVE: Head and neck squamous cell carcinoma (HNSCC) patients with N3 neck disease at presentation are the minority. Prognosis for such patients is poor, but there is disagreement about which treatment policy is best adopted. The aim of this study was to identify which groups of patients are best offered radical treatment, examining factors of association, prognosis, and survival. STUDY DESIGN: Prospective cohort study. SETTING: Regional tertiary head and neck cancer unit. SUBJECTS AND METHODS: Data were collected prospectively from patients treated for HNSCC with N3 nodal disease between 1975 and 2005. The data collected included age, sex, tumor TNM stage, histological grade, treatment, and survival. Odds ratio was used to calculate whether each parameter was statistically significant. Tumor-specific and observed survival curves were also calculated. RESULTS: A total of 275 patients had N3 disease. Multivariate analysis confirmed that advanced disease at the primary site (odds ratio = 4.6, P = .0261) mitigated against curative treatment. Comparison of tumor-specific survival between curative and palliative treatment strategies suggests that aggressive treatment is associated with greatly improved survival (median survival = 1.45 years, 95% confidence interval [CI] = 1.23-1.67 years; 5-year survival = 26.6%, CI = 17.14%-36.06%) compared with those treated palliatively (median survival = 3.18 months, CI = 3.06-3.30 months; no 5-year survivors; P < .0001). CONCLUSION: A major factor in determining treatment strategies for N3 disease HNSCC is the extent of disease at the primary site. These data suggest that aggressive treatment of the neck improves survival and should be considered in these patients.