adjuvant therapy who underwent RP were included. The median age was 64.7 years, the median preoperative PSA level was 7.9 ng/ mL, and the median follow-up was 5.2 years. We analysed pathological tumour stage, grading, number and location of PSMs, PSAfree survival, local recurrence-free survival, metastasis-free survival, prostate cancerspecific and, overall survival prospectively. RESULTSThe overall rate of PSMs was 17.2%. The number was higher in higher stage ( P < 0.001) and higher grade tumours ( P = 0.041). For a PSM the PSA recurrence rate was 64.3%, the local recurrence rate was 18.6%, the development of distant metastasis was 15.7% and therefore much higher than in patients with negative margins (20.5%, 2.7%, and 1.5%). A PSM was an adverse predictor for PSA-free survival ( P < 0.001), local recurrence-free survival ( P = 0.002), and development of metastasis ( P = 0.003) on multivariate analysis. The number and location of PSMs was of no additional prognostic value. CONCLUSIONS

OBJECTIVE To assess whether under‐ or overweight at the time of surgery has any effect on the survival of the patients with renal cell carcinoma (RCC), as obesity increases the risk of developing RCC. PATIENTS AND METHODS We prospectively evaluated 780 patients who had nephrectomy for RCC between 1990 and 2005. We used uni‐ and multivariate Cox proportional hazards models to assess the effect of body mass index (BMI), tumour stage, Fuhrman grade, age, sex, histological type and performance status on cancer‐specific survival (CSS). Patients were grouped according to BMI (in kg/m2), as underweight (<18.5), normal (18.5–<25), overweight (25–<30) and obese (≥30). RESULTS The median (range) follow‐up was 5.3 (0.5–15.4) years, the patients being followed until June 2006; 254 patients died during the follow‐up. Multivariate analyses of all patients showed that tumour stage, Fuhrman grade, Karnofsky performance status, age, sex and BMI were independent prognostic factors for CSS. While underweight patients had a significantly worse prognosis than those of normal weight, overweight or obese patients had a similar outcome to that of patients of normal weight. In a subgroup analyses including patients with localized RCC only, there was a strong tendency to less aggressive disease in the overweight group (P = 0.081). CONCLUSIONS Being underweight is an unfavourable and new risk factor for CSS in patients with RCC treated by nephrectomy. Although not significant, there seems to be a limited favourable prognostic effect of overweight on CSS in patients with localized RCC.

The enhancer of zeste homolog 2 (EZH2) gene has been recently linked to human malignancies where it may serve as a new target for cancer therapy. Here, we analyzed EZH2 expression in primary renal cell carcinoma (RCC) specimens and in nontumorous tissue samples from adult kidney. EZH2 transcripts were detectable in all RCC specimens examined. Expression levels were significantly higher in tumor tissue (p 0.0001) than in samples from normal adult kidney. Moreover, inhibition of endogenous EZH2 expression in RCC cell lines by RNA interference (RNAi) led to reduced proliferation and increased apoptosis in RCC cells. These data show that EZH2 is overexpressed in RCC. Furthermore, they indicate that the EZH2 gene plays a role for both the proliferation and the apoptosis resistance of RCC cells. Targeted inhibition of EZH2 could therefore represent a novel strategy to improve the therapeutic response of RCC. ' 2008 Wiley-Liss, Inc.Key words: renal cell carcinoma; enhancer of zeste homolog 2 (EZH2); RNA interference; tumor therapy Renal cell carcinoma (RCC) is estimated to account for more than 51,000 new cases and almost 13,000 cancer-related deaths in the United States in 2007, making it the second most lethal of the urological cancers. 1 RCCs typically are highly resistant toward chemotherapy with a concomitant poor prognosis in advanced stages. 2 Therefore, the identification of novel therapeutic targets and the development of new strategies for RCC treatment are urgently required.The enhancer of zeste homolog 2 (EZH2) gene encodes a polycomb group (PcG) protein, which acts as a histone methyltransferase 3-5 and also can directly control DNA methylation. 6 EZH2 is involved in several key regulatory mechanisms within eukaryotic cells, such as control of embryonal development or cell proliferation. 7,8 Moreover, there is accumulating evidence indicating that EZH2 may also play a pivotal role in the etiology of several tumor forms, which include prostate cancer 9,10 and breast cancer. 10,11 For both of these cancers, EZH2 expression is often observed in proliferative and more aggressive tumor subgroups and has diagnostic and/or prognostic value. [9][10][11] Notably, however, EZH2 appears to be not only a potential tumor marker but may itself contribute to the deregulation of cell growth as a bona fide oncogene. Overexpression of EZH2 conferred cellular growth advantage in vitro, 11-13 promoted invasion 11 and exhibited oncogenic properties in nude mice. 14 Vice versa, inhibition of EZH2 expression by antisense constructs or RNA interference (RNAi) did result in growth inhibition of some cancer cells. 9,15 Furthermore, RNAi-mediated inhibition of EZH2 expression induced anoikis in circulating prostate carcinoma precursor cells 16 and apoptotic cell death in breast cancer cells. 17 A possible role of EZH2 for RCC has not been studied so far. Here, we analyzed EZH2 expression in primary RCC specimens and in nontumorous tissue. In addition, we investigated the functional role of EZH2 for the proliferation control and apop...

effects of PN, RS or RS + PN fat infiltration, univariable and multivariable Cox proportional hazard regression models were applied, including lymph node status, metastases, presence of sarcomatoid features and tumour necrosis, Fuhrman's grade, Karnofsky performance status, and tumour size. RESULTSPN fat invasion alone was present in 58, RS in 21, and PN + RS in 27 patients. The median follow-up was 2.9 years; 49 patients died from RCC. In univariable and multivariable analyses RS fat infiltration was an unfavourable prognostic factor (adjusted hazard ratio, HR, 2.24, P = 0.019). Univariable analysis of RS + PN fat infiltration showed the worst prognostic effect (HR 3.25, P < 0.001). In multivariable analysis this combination was an independent prognostic factor (HR 2.75, P = 0.007), as was the presence of metastasis (HR 5.64, P < 0.001). In this group of RS + PN fat infiltration the 5-year cancer-specific survival was 31%. CONCLUSIONUnivariable and multivariable analyses showed that the combination of RS and PN fat infiltration is an independent unfavourable prognostic marker. We recommend that perirenal fat infiltration should be further differentiated into RS fat or PN infiltration in the TNM classification. This will better stratify patient prognosis and might allow those in need of adjuvant therapy to be identified. KEYWORDSrenal cell cancer, stage pT3a, perirenal, fat infiltration, renal sinus Study Type -Prognostic (case series) Level of Evidence 4 OBJECTIVETo evaluate the influence of perinephric (PN) and renal sinus (RS) fat infiltration on cancer-specific survival beyond other prognostic factors, as the Tumour-NodeMetastasis (TNM) classification system defines stage T3a renal cell carcinoma (RCC) as infiltration of perirenal fat and/or direct infiltration of the adrenal gland. Perirenal fat invasion is differentiated into RS and PN fat infiltration, but not further classified for the prognosis.