-
Andrea Camerini,
Sara Donati,
Paolo Viacava,
Olimpia Siclari,
Cheti Puccetti,
Gianna Tartarelli,
Chiara Valsuani, Filomena De Luca,
Leonardo Martini,
Andrea Cavazzana,
Domenico Amoroso
[show abstract]
[hide abstract]
ABSTRACT: The human epidermal growth factor receptor 2 (HER2) and p53 pathways may be involved in chemotherapy sensitivity and/or resistance. We explore the value of HER2 and p53 status to foretell docetaxel sensitivity in advanced breast cancer.
HER2 and p53 expression was analysed in 36 (median age 55 yrs; range 37-87) metastatic breast cancer patients receiving docetaxel-based first-line chemotherapy. HER2 was determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), p53 was tested by IHC. We correlate the expression of study parameters with pathologic parameters, RECIST response and survival. The standard cut-off value of 2 was used to determine HER2 overexpression while p53 mean expression level was used to divide low/high expressors tumors.
Median time to progression and overall survival were 9 (range 2-54) and 20 (range 3-101) months. Overall response rate was 41.6%. Nine cases showed HER2 overexpression. HER2 was more frequently overexpressed in less differentiated (p=0.05) and higher stage (p=0.003) disease. Mean FISH-HER2 values were significantly higher in responder than in non-responder pts (8.53±10.21 vs 2.50±4.12, p=0.027). Moreover, HER2 overexpression correlates with treatment response at cross-tabulation analysis (p=0.046). p53 expression was only associated with higher stage disease (p=0.02) but lack of any significant association with HER status or docetaxel response. No significant relation with survival was observed for any parameter.
Our data seem to indicate that FISH-determined HER2 status but not p53 is associated with docetaxel sensitivity in metastatic breast cancer.
Journal of Experimental & Clinical Cancer Research 01/2011; 30:38. · 2.15 Impact Factor
-
Alessandro Sgambato,
Andrea Camerini,
Giannicola Genovese, Filomena De Luca,
Paolo Viacava,
Mario Migaldi,
Alma Boninsegna,
Massimo Cecchi,
Carlo A Sepich,
Giulio Rossi,
Vincenzo Arena,
Achille Cittadini,
Domenico Amoroso
[show abstract]
[hide abstract]
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 α-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 α-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 α-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.
Cancer Science 09/2010; 101(9):2080-6. · 3.33 Impact Factor
-
Alessandro Sgambato,
Andrea Camerini,
Domenico Amoroso,
Giannicola Genovese, Filomena De Luca,
Massimo Cecchi,
Mario Migaldi,
Alessandro Rettino,
Chiara Valsuani,
Gianna Tartarelli,
Sara Donati,
Olimpia Siclari,
Giulio Rossi,
Achille Cittadini
[show abstract]
[hide abstract]
ABSTRACT: The dystroglycan (DG) complex is a transmembrane glycoprotein that forms a continuous link from the extracellular matrix to the actin cytoskeleton. Deregulated expression of DG has been reported in a variety of human malignancies and related to tumor aggressiveness. In this study expression of the DG subunit was evaluated by immunostaining in a series of renal epithelial cancers and its relation with traditional prognostic indicators and with the clinical outcome of the patients was evaluated. alphaDG expression was undetectable in a significant fraction of tumors (54%). In renal cell carcinomas (RCC) loss of alpha-DG staining correlated with higher tumor grade (p = 0.02) but not with tumor stage nor tumor size. In clear cell RCC patients loss of alphaDG staining correlated with an increased risk of recurrence (p = 0.002 by log-rank test) and death (p = 0.004) also when patients with lower grade or stage tumors were analyzed separately. In a multivariate analysis loss of DG staining confirmed to be and independent predictor of shorter disease-free (p = 0.001; RR = 4.9) and overall (p = 0.009; RR = 4.9) survival stronger than tumor grade and size. These findings demonstrate that loss of alphaDG expression, which correspond to loss of a functional DG complex, is a frequent event in human renal tumorigenesis and is an independent predictor of early recurrence and death for patients with clear cell RCC.
Cancer biology & therapy 01/2008; 6(12):1840-6. · 2.64 Impact Factor
