RESUMO
BACKGROUND: Spindle checkpoint proteins such as Mad2 and BubR1 are important for chromosome segregation during mitosis. The aim of the present study was to examine their possible impact on prognosis in tonsillar carcinomas and their relation to clinical variables, the prevalence of human papillomavirus (HPV), p53 status, and Ki-67 positivity. METHODS: We examined the expression of Mad2 and BubR1 by immunohistochemistry on tissue microarrays from 105 patients with tonsillar carcinomas. RESULTS: BubR1 and Mad2 were both expressed in tonsillar carcinomas. Expression of BubR1 was a significant prognostic factor in univariate survival analysis. In multivariate analyses, BubR1 was a significant prognostic factor together with stage, age, and HPV status p < .01), whereas Mad2 did not show any significant correlations. CONCLUSION: We have shown that BubR1 expression is a novel and strong prognostic factor in tonsillar carcinomas, giving additional information to the TNM stage and other known prognostic factors.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Proteínas Serina-Treonina Quinases/metabolismo , Neoplasias Tonsilares/metabolismo , Neoplasias Tonsilares/mortalidade , Fatores Etários , Proteínas de Ligação ao Cálcio/metabolismo , Carcinoma de Células Escamosas/patologia , Proteínas de Ciclo Celular/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Proteínas Mad2 , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Infecções por Papillomavirus/epidemiologia , Prognóstico , Proteínas Repressoras/metabolismo , Neoplasias Tonsilares/patologiaRESUMO
CONCLUSIONS: This study confirms a high prevalence of human papillomavirus (HPV)-positive tonsillar tumours (52%). The survival of the HPV-positive group was significantly better in males. OBJECTIVES: We assessed the prevalence of HPV in 137 patients with tonsillar carcinomas, measured the p53- and Ki-67-positive tumour cell fractions and correlated the results with clinical variables. PATIENTS AND METHODS: Tumour DNA from patients with squamous cell carcinoma of the tonsillar region was amplified by PCR and sequenced for detection of HPV subtypes. RESULTS: HPV was found in 71/137 (52%) of the tumours; HPV-16 was the most frequent subtype (87%). HPV positivity did not correlate with gender, stage, T- and N categories, Ki-67 expression or p53 positivity. The HPV-positive group had a significantly better survival (p < 0.01) compared with the HPV-negative group in males. In a multivariate analysis HPV status gave prognostic information in addition to the earlier established factors, i.e. age, gender and stage (p < 0.05).
Assuntos
Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/virologia , Papillomavirus Humano 16/isolamento & purificação , Papiloma/epidemiologia , Papiloma/virologia , Neoplasias Tonsilares/epidemiologia , Neoplasias Tonsilares/virologia , Idoso , Biópsia , Carcinoma de Células Escamosas/genética , Feminino , Genes p53/genética , Humanos , Imuno-Histoquímica , Incidência , Antígeno Ki-67/genética , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Tonsila Palatina/patologia , Tonsila Palatina/virologia , Papiloma/genética , Prevalência , Prognóstico , Neoplasias Tonsilares/genéticaRESUMO
BACKGROUND: Several modifications of the TNM system have been reported as better prognostic tools than the original classification in head and neck cancer, but none of these modifications has been tested in a large series of tonsillar carcinomas. These studies did not examine host and treatment factors as predictors in addition to TNM. METHODS: Three hundred and ten consecutively untreated patients with squamous cell carcinoma of the tonsillar region admitted to the Norwegian Radium Hospital and/or the National Hospital between 1960 and 1996 were included. RESULTS: The five reported TN-based stage modifications were all highly significant predictors of survival. Four clinical variables indicating shorter disease-specific survival were identified: age > 60, male gender, total radiation dose < 70 Gy, and duration of radiotherapy > 50 days. CONCLUSIONS: Earlier reported TNM-based stage modifications are all very useful predictors of survival in tonsillar carcinomas. In addition, age, gender, total radiation dose, and duration of radiotherapy were important prognostic factors. We propose that both host and treatment factors should be tested carefully when building new prognostic indices in tonsillar carcinomas.
