RESUMEN
BACKGROUND: Human papillomavirus (HPV) is the major predictor of outcome in oropharyngeal squamous cell carcinoma (OSCC) but the disease is heterogeneous and there is limited understanding of the prognostic significance of other molecular markers in relation to HPV. This multi-institutional, retrospective study examined the prognostic significance of Ki67 expression in association with HPV status in OSCC. METHODS: The 105 patients recruited had a median follow-up of 70 months. Tumor HPV status was determined by HPV E6-targeted multiplex real-time polymerase chain reaction/p16 semiquantitative immunohistochemistry and Ki67 expression by semiquantitative immunohistochemistry. Determinants of recurrence and mortality hazards were modelled using Cox regression with censoring at dates of last follow-up. RESULTS: HPV and Ki67 positivity rates were 46 and 44 %, respectively. HPV-positive cancers were more likely to be Ki67-positive. On multivariate analysis, both HPV and Ki67 were predictors of outcome. Ki67-positive cancers were associated with a 3.13-fold increased risk of disease-related death compared with Ki67-negative cancers. Among HPV-negative patients, Ki67-positive disease was associated with 5.6-fold increased risk of oropharyngeal cancer-related death (p = 0.002), 5.5-fold increased risk of death from any cause (p = 0.001), and 2.9-fold increased risk of any event (p = 0.013). The risk of locoregional failure was lowest in patients with HPV-positive/Ki67-positive cancers. CONCLUSIONS: Ki67 predicts disease-related death in oropharyngeal cancer independent of HPV status. A combination of Ki67 and HPV status provides improved prognostic information relative to HPV status alone. Our data suggest, for the first time, that Ki67 status has prognostic value, particularly in HPV-negative oropharyngeal cancer.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/metabolismo , Antígeno Ki-67/metabolismo , Recurrencia Local de Neoplasia/metabolismo , Neoplasias Orofaríngeas/metabolismo , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/virología , ADN Viral/genética , Femenino , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/virología , Estadificación de Neoplasias , Neoplasias Orofaríngeas/mortalidad , Neoplasias Orofaríngeas/patología , Neoplasias Orofaríngeas/virología , Papillomaviridae/genética , Infecciones por Papillomavirus/mortalidad , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/virología , Pronóstico , Reacción en Cadena en Tiempo Real de la Polimerasa , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
The transformation of melanocytes to melanoma cells is characterised by abnormal proliferation resulting from alterations in cell cycle regulatory mechanisms. This occurs through alterations in the two major cell cycle regulatory pathways, the retinoblastoma (Rb) and p53 tumour suppressor pathways. This review summarises the current knowledge of alterations in these two pathways at G1/S transition and specifically the role of the key cell cycle regulatory proteins pRb, p16INK4a (p16), cyclin D1, p27Kip1 (p27), p53 and p21Waf1/Cip1 (p21) in the pathogenesis of melanoma. It also considers their prognostic significance. Current data indicate that alterations of cyclin kinase inhibitor (cdki) levels are implicated in the pathogenesis of melanoma and may be useful prognostic markers. However, large validation studies linked to comprehensive clinical follow up data are necessary to clarify the prognostic significance of cell cycle regulatory proteins in individual patients.
Asunto(s)
Proteínas de Ciclo Celular/fisiología , Ciclo Celular/fisiología , Melanoma/fisiopatología , Neoplasias Cutáneas/fisiopatología , Animales , Ciclo Celular/genética , Proteínas de Ciclo Celular/genética , Proliferación Celular , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/patología , Ciclina D1/genética , Ciclina D1/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica/genética , Regulación Neoplásica de la Expresión Génica/fisiología , Humanos , Melanoma/genética , Pronóstico , Proteína de Retinoblastoma/genética , Proteína de Retinoblastoma/metabolismo , Neoplasias Cutáneas/genética , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
Cimetidine is known to have immunomodulatory effects and this study aimed to examine the effect of pre-operative cimetidine treatment on lymphocytic infiltration in n = 72 women with breast cancer randomised to 400 mg bd or placebo for five days presurgery. A combined index was devised by adding infiltrating lymphocyte percentage and lymphoid score. There were no significant differences in circumferential infiltrate and lymphoid follicles in cimetidine treated patients and control patients with breast cancer.