Expression levels of p27kip1, 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 p27kip1 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 p27kip1 was reduced in a significant fraction of tumors and low p27kip1 staining correlated with higher tumor grade (P < 0.01). Recurrence and death from clear cell RCCs were significantly more frequent in p27kip1‐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 p27kip1 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 p27kip1. Loss of nuclear p27kip1 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 Sci 2010; 00: 000–000)
Gleason score has been identified as an important variable to predict disease extent and biologic behaviour of prostate cancer. However, the correlation between Gleason score of needle biopsy and surgical specimen is often poor. We studied 72 patients who underwent needle biopsy and radical prostatectomy to correlate Gleason score with PSA, clinical and pathological tumour stage. Only 47.2% of Gleason scores were identical in the biopsy and specimens, 37.5% were undergraded and 15.2% were overgraded. Correlations between clinical and pathological stage were identical in 30.5% of patients, 61.1% of patients were understaged and 8.3% overstaged. In conclusion, accuracy of clinical staging and grading of prostate cancer is low. Although the Gleason score on needle biopsy might be useful to predict the final stage and grade, correlation with surgical specimen is poor.
BackgroundBladder cancer (BC) is the 9th most common cancer diagnosis worldwide. Low grade (LG) represents 70% of all BCs, characterized by recurrence and rare ability (10–15%) to progress to high grade (HG) and invade. The remaining 30% is high grade (HG), fast invasive BC, which is resistant to therapy. Identifying biomarkers for predicting those tumors able to progress is a key goal for patient outcome improvement. This study focuses on the most promising prognostic markers.Materials and methodsTP53 and FGFR3 mutational status, Survivin, CK19, CK20, E-cadherin and CD44 gene expression analysis were performed on 66 BCs.ResultsSurvivin was found associated to tumor grade (p<0.05). Moreover, Survivin correlated with CD44 in TP53 wild type (p = 0.0242) and FGFR3 wild type (p = 0.0036) tumors. In particular the Survivin-CD44 correlation was associated to HG FGFR3 wild type BCs (p = 0.0045). Unsupervised hierarchical clustering based on gene expression data identified four distinct molecular groups reflecting the patient histology (p = 0.038).ConclusionWe suggest Survivin, both as a biomarker associated to G3 BCs but negatively related to TP53 mutational status, and as a potential novel therapeutic target.
The use of absorbable staples may allow to reduce the operating time of orthotopic bladder replacement. We report our experience in 14 patients with a modification of the Studer technique using absorbable PolyGIA instruments. The technique has been shown to be simple and quick to perform (time for pouch creation 15-40 minutes, mean 16 minutes) with no significant intraoperative difficulties. Urodynamic data and continence are satisfactory and seem comparable to different procedures and not related to staples' use. The main question remains if the reduced operating time equalizes the high cost of staple devices.
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