ABSTRACT
We investigated the expression of Aurora kinases A and B by immunohistochemistry in 68 ovarian carcinomas to analyze their prognostic value. The amplification of AURKA gene by fluorescence in situ hybridization was also assessed. Overall, 58.8% and 85.3% of ovarian carcinomas showed expression of Aurora A and B, respectively. Amplification of AURKA was found in 27.6% of cases examined. Tumors with Aurora A expression showed a lower rate of recurrence than those tumors without Aurora A expression (65% versus 91.7%, P = .019). In the univariate analysis, patients with Aurora A and B expression showed an increased progression-free survival (P = .023 and .06, respectively, log-rank test) and overall survival (P = .03 and .02, respectively, log-rank test). The multivariate analysis adjusted to optimal surgery by Cox proportional hazards regression showed Aurora A expression as an independent prognostic factor for progression-free survival (P = .03) and overall survival (P = .02). In conclusion, Aurora A expression seems to have a prognostic value in ovarian carcinoma.
Subject(s)
Biomarkers, Tumor/analysis , Ovarian Neoplasms/enzymology , Protein Serine-Threonine Kinases/biosynthesis , Adult , Aged , Aged, 80 and over , Aurora Kinase A , Aurora Kinases , DNA Mutational Analysis , Disease-Free Survival , Female , Gene Amplification , Gene Expression , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Kaplan-Meier Estimate , Middle Aged , Ovarian Neoplasms/genetics , Ovarian Neoplasms/mortality , Prognosis , Protein Serine-Threonine Kinases/genetics , Tissue Array Analysis , Tumor Suppressor Protein p53/geneticsABSTRACT
Reactive Oxygen Species (ROS) result from cell metabolism as well as from extracellular processes. ROS exert some functions necessary for cell homeostasis maintenance. When produced in excess they play a role in the causation of cancer. ROS mediated lipid peroxides are of critical importance because they participate in chain reactions that amplify damage to biomolecules including DNA. DNA attack gives rise to mutations that may involve tumor suppressor genes or oncogenes, and this is an oncogenic mechanism. On the other hand, ROS production is a mechanism shared by many chemotherapeutic drugs due to their implication in apoptosis control. The ROS mediated cell responses depend on the duration and intensity of the cells exposing to the increased ROS environment. Thus the status redox is of great importance for oncogenetic process activation and it is also implicated in tumor susceptibility to specific chemotherapeutic drugs. Phospholipid Hydroperoxide Glutathione Peroxidase (PH-GPx) is an antioxidant enzyme that is able to directly reduce lipid peroxides even when they are bound to cellular membranes. This article will review the relevance of oxidative stress, particularly of lipid peroxidation, in cell response with special focus in carcinogenesis and cancer therapy that suggests PH-GPx as a potentially important enzyme involved in the control of this processes.
