BACKGROUND: Somatic alteration of the von Hippel-Lindau disease tumor suppressor gene (VHL) is one of the most common genetic changes observed in the sporadic, clear-cell subtype of renal cell carcinoma (RCC). However, the prognostic utility of VHL mutations has not been examined. The purpose of this study was to explore the association between VHL mutations and the risk of death from sporadic clear-cell RCC. METHODS: A total of 187 Japanese patients with clear-cell RCC who underwent nephrectomy from October 1986 through December 1995 were examined for somatic VHL gene alteration. Clinicopathologic and survival data were also collected. Kaplan-Meier analyses and Cox proportional hazards models were used to explore associations. All statistical tests were two-sided. RESULTS: A VHL alteration (mutation or hypermethylation) was detected in 108 RCC tumor samples: intragenic mutations in 98 (52%) and hypermethylation in 10 (5.3%). VHL alterations were strongly associated with better cancer-free survival and cancer-specific survival for the 134 patients with stage I-III clear-cell RCC treated by radical nephrectomy (log-rank P =.024 and.023, respectively). These associations were more statistically significant among patients with relatively advanced disease (stage III [P =.014 and.010, respectively] or stage II + III [P =.002 and.009]) or higher grade tumors (G3 or higher [P =.013 and.032] or G2 or higher [P =.013 and.018]) and among patients who presented with symptoms (P =.005 and.012). VHL alterations remained an independent prognostic factor for patients with stage I-III tumors after adjustment for sex, age, stage, grading, and symptomatic presentation. VHL alterations were not associated with cancer-specific survival for the 53 patients with stage IV tumors treated with palliative or adjunctive nephrectomy (log-rank P =.760). CONCLUSION: The VHL alteration status may provide useful prognostic information, as a biomolecular marker, for patients with stage I-III clear-cell RCC who have undergone nephrectomy.
BACKGROUND: Somatic alteration of the von Hippel-Lindau disease tumor suppressor gene (VHL) is one of the most common genetic changes observed in the sporadic, clear-cell subtype of renal cell carcinoma (RCC). However, the prognostic utility of VHL mutations has not been examined. The purpose of this study was to explore the association between VHL mutations and the risk of death from sporadic clear-cell RCC. METHODS: A total of 187 Japanese patients with clear-cell RCC who underwent nephrectomy from October 1986 through December 1995 were examined for somatic VHL gene alteration. Clinicopathologic and survival data were also collected. Kaplan-Meier analyses and Cox proportional hazards models were used to explore associations. All statistical tests were two-sided. RESULTS: A VHL alteration (mutation or hypermethylation) was detected in 108 RCC tumor samples: intragenic mutations in 98 (52%) and hypermethylation in 10 (5.3%). VHL alterations were strongly associated with better cancer-free survival and cancer-specific survival for the 134 patients with stage I-III clear-cell RCC treated by radical nephrectomy (log-rank P =.024 and.023, respectively). These associations were more statistically significant among patients with relatively advanced disease (stage III [P =.014 and.010, respectively] or stage II + III [P =.002 and.009]) or higher grade tumors (G3 or higher [P =.013 and.032] or G2 or higher [P =.013 and.018]) and among patients who presented with symptoms (P =.005 and.012). VHL alterations remained an independent prognostic factor for patients with stage I-III tumors after adjustment for sex, age, stage, grading, and symptomatic presentation. VHL alterations were not associated with cancer-specific survival for the 53 patients with stage IV tumors treated with palliative or adjunctive nephrectomy (log-rank P =.760). CONCLUSION: The VHL alteration status may provide useful prognostic information, as a biomolecular marker, for patients with stage I-III clear-cell RCC who have undergone nephrectomy.
Authors: Ying Yi; Olga Mikhaylova; Aygun Mamedova; Prabhat Bastola; Jacek Biesiada; Enas Alshaikh; Linda Levin; Rachel M Sheridan; Jarek Meller; Maria F Czyzyk-Krzeska Journal: Clin Cancer Res Date: 2010-10-26 Impact factor: 12.531
Authors: Mariana Rezende Alves; Felipe Cavalcanti Carneiro; André Mourão Lavorato-Rocha; Walter Henriques da Costa; Isabela Werneck da Cunha; Stênio de Cássio Zequi; Gustavo Cardoso Guimaraes; Fernando Augusto Soares; Dirce Maria Carraro; Rafael Malagoli Rocha Journal: Virchows Arch Date: 2014-07-16 Impact factor: 4.064
Authors: Luciana Schultz; Alcides Chaux; Roula Albadine; Jessica Hicks; Jenny J Kim; Angelo M De Marzo; Mohamad E Allaf; Michael A Carducci; Ronald Rodriguez; Hans-Joerg Hammers; Pedram Argani; Victor E Reuter; George J Netto Journal: Am J Surg Pathol Date: 2011-10 Impact factor: 6.394
Authors: Olga Mikhaylova; Monika L Ignacak; Teresa J Barankiewicz; Svetlana V Harbaugh; Ying Yi; Patrick H Maxwell; Martin Schneider; Katie Van Geyte; Peter Carmeliet; Monica P Revelo; Michael Wyder; Kenneth D Greis; Jarek Meller; Maria F Czyzyk-Krzeska Journal: Mol Cell Biol Date: 2008-02-19 Impact factor: 4.272