RESUMEN
The retinoblastoma family members--pRb, pRb2/p130 and p107--are tumor suppressor genes involved in controlling four major cellular processes: growth arrest, apoptosis, differentiation and angiogenesis. Molecular genetic studies have identified abnormalities of these tumor suppressor genes in a large proportion of human cancers. These genetic alterations have emerged as significant factors in the pathogenesis and progression of many types of tumors and are therefore likely to provide relevant information to assess risk in cancer patients. There is a pressing clinical need to identify prognostic and predictive factors for patients with cancer, because there is an undeniable importance in being able to determine which patients will have a favorable outcome without further therapy (prognostic factor) and which will need some additional treatment (predictive factor). This review examines the predictive and/or prognostic role of each retinoblastoma family member in human cancer.
Asunto(s)
Genes de Retinoblastoma , Neoplasias de la Retina/genética , Proteína de Retinoblastoma/genética , Retinoblastoma/genética , Femenino , Neoplasias Gastrointestinales/genética , Neoplasias de los Genitales Femeninos/genética , Neoplasias de Cabeza y Cuello/genética , Neoplasias Hematológicas/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Ováricas/genética , Pronóstico , Sarcoma/genética , Neoplasias Urológicas/genéticaRESUMEN
Few biological parameters have been shown to have a prognostic role in patients with advanced ovarian cancer. p27Kip1 is a cyclin-dependent kinase inhibitor, and its loss may contribute to tumor progression. We determined whether p27Kip1 protein expression in advanced ovarian cancer could be associated with prognosis. p27Kip1 status was assessed by immunohistochemical analysis of tissue sections from primary tumors of 99 patients with stages III-IV ovarian carcinoma and was analyzed in relation to clinicopathological variables, time to progression (TTP), and overall survival (OS). p27Kip1 expression was detected in 47 (47%) of the 99 patients. p27 expression did not correlate with any of the classical clinicopathological parameters. Loss of p27 protein was significantly associated with a short TTP (P = 0.0004) and decreased OS (P = 0.0302). The 5-year TTP rate in p27-positive patients was 50% versus 11% in p27-negative patients. p27-positive cases showed a 5-year OS rate of 53% compared with 43% of p27-negative cases. In multivariate analysis, p27 expression was an independent predictor of progression of disease (P = 0.0009) and survival (P = 0.0032) when considered together with stage of disease, presence of ascites, and residual tumor at surgery. Loss of p27Kip1 conferred poor prognosis independently of proliferative index, as assessed by proliferating cell nuclear antigen immunostaining. p27 immunoreactivity can be used to predict progression of disease and survival in patients with advanced epithelial ovarian cancer and therefore may represent a new prognostic marker.