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Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of the human telomerase and plays a key role in telomere restitution and gene regulation. Evidence suggests that hTERT is linked with the risk and progression of several malignancies, but there are no comprehensive data in renal cell carcinoma (RCC). In this case-control study, we assessed seven polymorphic hTERT gene variants (MNS16A, rs2736100, rs2736098, rs7726159, rs2853677, rs13172201, and rs10069690), hTERT serum levels, and the telomere length of 663 individuals, including 243 with clear cell RCC and 420 age- and gender-matched healthy controls. The SL and SS genotypes of MNS16A were associated with a decreased risk for RCC on the multivariable logistic regression analysis (SL-OR 0.72, SS-OR 0.37, P

Objective To validate Caveolin-1 as an independent prognostic marker of biochemical recurrence (BCR) in a large multi-institutional cohort of patients with prostate cancer treated with radical prostatectomy (RP). Patients and Methods Caveolin-1 expression was evaluated by immunochemistry on a tissue microarray in 3 117 patients treated with RP for prostate cancer at five institutions. Univariable and multivariable Cox proportional hazards regression models assessed the association of Caveolin-1 status with BCR. Harrell's c-index quantified prognostic accuracy. Results Caveolin-1 was overexpressed in 644 (20.6%) patients and was associated with higher pathological Gleason sum (P = 0.002) and lymph node metastases (P = 0.05). Within a median (interquartile range) follow-up of 38 (21–66) months, 617 (19.8%) patients experienced BCR. Patients with overexpression of Caveolin-1 had worse BCR-free survival than those with normal expression (log-rank test, P = 0.004). Caveolin-1 was an independent predictor of BCR in multivariable analyses that adjusted for the effects of standard clinicopathological features (hazard ratio 1.21, P = 0.037). Addition of Caveolin-1 in a model for prediction of BCR based on these standard prognosticators did not significantly improve the predictive accuracy of the model. In subgroup analyses, Caveolin-1 was associated with BCR in patients with favourable pathological features (pT2pN0 and Gleason score = 6; P = 0.021). Conclusions We confirmed that overexpression of Caveolin-1 is associated with adverse pathological features in prostate cancer and independently predicts BCR after RP, especially in patients with favourable pathological features. However, it did not add prognostically relevant information to established predictors of BCR, limiting its use in clinical practice.

Objective To compare outcomes of patients with lymph node (LN)-positive urothelial carcinoma of the bladder (UCB) treated with or without cisplatin-based combined adjuvant chemotherapy (AC) after radical cystectomy (RC). Patients and Methods We retrospectively analysed 1523 patients with LN-positive UCB, who underwent RC with bilateral pelvic LN dissection. All patients had no evidence of disease after RC. AC was administered within 3 months. Competing-risks models were applied to compare UCB-related mortality. Results Of the 1523 patients, 874 (57.4%) received AC. The cumulative 1-, 2- and 5-year UCB-related mortality rates for all patients were 16%, 36% and 56%, respectively. Administration of AC was associated with an 18% relative reduction in the risk of UCB-related death (subhazard ratio 0.82, P = 0.005). The absolute reduction in mortality was 3.5% at 5 years. The positive effect of AC was detectable in patients aged ≤70 years, in women, in pT3–4 disease, and in those with a higher LN density and lymphovascular invasion. This study is limited by its retrospective and non-randomised design, selection bias, the absence of central pathological review and lack in standardisation of LN dissection and cisplatin-based protocols. Conclusion AC seems to reduce UCB-related mortality in patients with LN-positive UCB after RC. Younger patients, women and those with high-risk features such as pT3–4 disease, a higher LN density and lymphovascular invasion appear to benefit most. Appropriately powered prospective randomised trials are necessary to confirm these findings.

Objective To assess the prognostic role of preoperative serum cholesterol in patients with renal cell carcinoma (RCC), as increasing evidence suggests that alterations in the lipid profile are associated with the development, progression and prognosis of various cancers. Patients and Methods We analysed 867 patients, who underwent radical or partial nephrectomy for RCC between 2002 and 2012. Preoperative total cholesterol levels were determined in serum using colorimetric analysis (CHOD-PAP method). The association with cancer-specific survival (CSS) was assessed with Cox models. Discrimination was quantified with the C-index. The median follow-up was 52 months. Results The median (interquartile range) serum cholesterol was 195 (166–232) mg/dL. Decreasing serum cholesterol was associated with more advanced T, N and M stages (P < 0.001), higher grades (P = 0.001) and presence of tumour necrosis (P = 0.002). Continuously coded cholesterol was associated with CSS in both univariable (hazard ratio [HR] 0.87, P < 0.001) and multivariable analyses (HR 0.93, P = 0.001). The discrimination of a multivariable base model increased significantly from 88.3% to 89.2% following inclusion of cholesterol (P = 0.006). In patients with clinically localised disease (T1–3N0/+M0), cholesterol remained associated with CSS in multivariable analysis (HR 0.90, P = 0.002) and increased the discrimination from 74.6% to 76.9% (P = 0.002). Conclusions Preoperative serum cholesterol is an independent prognostic factor for patients with RCC, with lower levels being associated with worse survival. Its use increases the discrimination of established prognostic factors. As cholesterol is a broadly available routine marker, its use may provide a meaningful adjunct in clinical practice. The biological rationale underlying this association remains to be clarified.