BACKGROUND: Mutations of the p53 gene are associated with a poor prognosis in several types of cancer. We investigated the prognostic importance of p53 mutations in patients with aggressive B-cell lymphoma. METHODS: We examined the relation between the presence or absence of a detectable p53 mutation in lymphoma cells and the response to chemotherapy and overall survival in 102 previously untreated patients with aggressive B-cell lymphoma. Mutations of the p53 gene were identified by polymerase-chain-reaction-mediated analysis of single-strand conformation polymorphisms and by direct sequencing. RESULTS: Of 102 cases of aggressive B-cell lymphoma, 22 (22 percent) involved p53 mutations. The rate of complete remission was significantly lower in patients with a tumor carrying a p53 mutation (6 of 22 patients, 27 percent) than in those with the wild-type p53 gene (61 of 80 patients, 76 percent) (P<0.001). Overall survival was significantly lower among patients with p53 mutations than among those with the wild-type p53 gene; the Kaplan-Meier estimates of survival at five years were 16 percent and 64 percent, respectively (P<0.001). Multivariate analysis incorporating prognostic factors from the international prognostic index demonstrated that p53 mutations had independent effects on the rates of complete remission and survival. When we categorized patients according to the international prognostic index, we found no effect of p53 mutations in patients in the groups at high-intermediate and high risk. However, these mutations were significantly associated (P< 0.001) with low rates of complete remission (33 percent vs. 91 percent) and survival (27 percent vs. 81 percent at five years) in the groups at low and low-intermediate risk. CONCLUSIONS: Mutations of the p53 gene are associated with a poor prognosis in patients with aggressive B-cell lymphoma.
BACKGROUND: Mutations of the p53 gene are associated with a poor prognosis in several types of cancer. We investigated the prognostic importance of p53 mutations in patients with aggressive B-cell lymphoma. METHODS: We examined the relation between the presence or absence of a detectable p53 mutation in lymphoma cells and the response to chemotherapy and overall survival in 102 previously untreated patients with aggressive B-cell lymphoma. Mutations of the p53 gene were identified by polymerase-chain-reaction-mediated analysis of single-strand conformation polymorphisms and by direct sequencing. RESULTS: Of 102 cases of aggressive B-cell lymphoma, 22 (22 percent) involved p53 mutations. The rate of complete remission was significantly lower in patients with a tumor carrying a p53 mutation (6 of 22 patients, 27 percent) than in those with the wild-type p53 gene (61 of 80 patients, 76 percent) (P<0.001). Overall survival was significantly lower among patients with p53 mutations than among those with the wild-type p53 gene; the Kaplan-Meier estimates of survival at five years were 16 percent and 64 percent, respectively (P<0.001). Multivariate analysis incorporating prognostic factors from the international prognostic index demonstrated that p53 mutations had independent effects on the rates of complete remission and survival. When we categorized patients according to the international prognostic index, we found no effect of p53 mutations in patients in the groups at high-intermediate and high risk. However, these mutations were significantly associated (P< 0.001) with low rates of complete remission (33 percent vs. 91 percent) and survival (27 percent vs. 81 percent at five years) in the groups at low and low-intermediate risk. CONCLUSIONS: Mutations of the p53 gene are associated with a poor prognosis in patients with aggressive B-cell lymphoma.
Authors: Jane N Winter; Shuli Li; Vikas Aurora; Daina Variakojis; Beverly Nelson; Maryla Krajewska; Lijun Zhang; Thomas M Habermann; Richard I Fisher; William R Macon; Mukesh Chhanabhai; Raymond E Felgar; Eric D Hsi; L Jeffrey Medeiros; James K Weick; Edie A Weller; Ari Melnick; John C Reed; Sandra J Horning; Randy D Gascoyne Journal: Clin Cancer Res Date: 2010-04-06 Impact factor: 12.531
Authors: Ken H Young; Dennis D Weisenburger; Bhavana J Dave; Lynette Smith; Warren Sanger; Javeed Iqbal; Elias Campo; Jan Delabie; Randy D Gascoyne; German Ott; Lisa Rimsza; H Konrad Müller-Hermelink; Elaine S Jaffe; Andreas Rosenwald; Louis M Staudt; Wing C Chan; Timothy C Greiner Journal: Blood Date: 2007-09-19 Impact factor: 22.113
Authors: Ali Karaman; Mehmet-Esref Kabalar; Onder Ozcan; Timur Koca; Dogan-Nasir Binici Journal: World J Gastroenterol Date: 2008-10-14 Impact factor: 5.742