Expression levels of p27(kip1), a negative regulator of the G1 phase of the cell cycle, and 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative DNA damage, were assessed by immunostaining in a series of renal cell carcinomas (RCCs) and their prognostic significance was evaluated. Expression of p27(kip1) as well as of the alpha-subunit of the dystroglycan (DG) complex, previously reported to be altered in RCC, was also evaluated by western blot analysis. Nuclear expression of p27(kip1) was reduced in a significant fraction of tumors and low p27(kip1) staining correlated with higher tumor grade (P < 0.01). Recurrence and death from clear cell RCCs were significantly more frequent in p27(kip1)-low expressing tumors and Kaplan-Meier curves showed a significant separation between high vs low expressor groups for both disease-free (P = 0.011) and overall (P = 0.002) survival. Low nuclear expression of p27(kip1) as well as loss of alpha-DG were confirmed to be independent prognostic parameters at a multivariate analysis and the simultaneous loss of both molecules defined a "high-risk" group of patients with increased risk of recurrence (RR = 28.7; P = 0.01) and death (RR = 12.9; P = 0.03). No significant correlation with clinical or pathological parameters was found for 8-OHdG staining. Western blot analyses suggested a post-translational mechanism for the loss of alpha-DG expression and demonstrated that cytoplasmic dislocation of the protein contributes to the loss of active nuclear p27(kip1). Loss of nuclear p27(kip1) is a frequent event in human RCCs and is a powerful predictor of poor outcome which, in combination with low DG expression, could help to identify high-risk patients with clear cell RCC.

Loss of nuclear p27(kip1) and alpha-dystroglycan is a frequent event and is a strong predictor of poor outcome in renal cell carcinoma / Sgambato, A; Camerini, A; Genovese, G; De Luca, F; Viacava, P; Migaldi, Mario; Boninsegna, A; Cecchi, M; Sepich, Ca; Rossi, G; Arena, V; Cittadini, A; Amoroso, D.. - In: CANCER SCIENCE. - ISSN 1347-9032. - ELETTRONICO. - 101:(2010), pp. 2080-2086. [10.1111/j.1349-7006.2010.01644.x]

Loss of nuclear p27(kip1) and alpha-dystroglycan is a frequent event and is a strong predictor of poor outcome in renal cell carcinoma.

MIGALDI, Mario;
2010

Abstract

Expression levels of p27(kip1), a negative regulator of the G1 phase of the cell cycle, and 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative DNA damage, were assessed by immunostaining in a series of renal cell carcinomas (RCCs) and their prognostic significance was evaluated. Expression of p27(kip1) as well as of the alpha-subunit of the dystroglycan (DG) complex, previously reported to be altered in RCC, was also evaluated by western blot analysis. Nuclear expression of p27(kip1) was reduced in a significant fraction of tumors and low p27(kip1) staining correlated with higher tumor grade (P < 0.01). Recurrence and death from clear cell RCCs were significantly more frequent in p27(kip1)-low expressing tumors and Kaplan-Meier curves showed a significant separation between high vs low expressor groups for both disease-free (P = 0.011) and overall (P = 0.002) survival. Low nuclear expression of p27(kip1) as well as loss of alpha-DG were confirmed to be independent prognostic parameters at a multivariate analysis and the simultaneous loss of both molecules defined a "high-risk" group of patients with increased risk of recurrence (RR = 28.7; P = 0.01) and death (RR = 12.9; P = 0.03). No significant correlation with clinical or pathological parameters was found for 8-OHdG staining. Western blot analyses suggested a post-translational mechanism for the loss of alpha-DG expression and demonstrated that cytoplasmic dislocation of the protein contributes to the loss of active nuclear p27(kip1). Loss of nuclear p27(kip1) is a frequent event in human RCCs and is a powerful predictor of poor outcome which, in combination with low DG expression, could help to identify high-risk patients with clear cell RCC.
101
2080
2086
Loss of nuclear p27(kip1) and alpha-dystroglycan is a frequent event and is a strong predictor of poor outcome in renal cell carcinoma / Sgambato, A; Camerini, A; Genovese, G; De Luca, F; Viacava, P; Migaldi, Mario; Boninsegna, A; Cecchi, M; Sepich, Ca; Rossi, G; Arena, V; Cittadini, A; Amoroso, D.. - In: CANCER SCIENCE. - ISSN 1347-9032. - ELETTRONICO. - 101:(2010), pp. 2080-2086. [10.1111/j.1349-7006.2010.01644.x]
Sgambato, A; Camerini, A; Genovese, G; De Luca, F; Viacava, P; Migaldi, Mario; Boninsegna, A; Cecchi, M; Sepich, Ca; Rossi, G; Arena, V; Cittadini, A; Amoroso, D.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/644775
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