Vimentin over-expression and carbonic anhydrase IX under-expression are independent predictors of recurrence, specific and overall survival in non-metastatic clear-cell renal carcinoma: a validation study.

PURPOSE: Clinical outcomes prognostic markers are awaited in clear-cell renal carcinoma (ccRCC) to improve patient-tailored management and to assess six different markers' influence on clinical outcomes from ccRCC specimen and their incremental value combined with TNM staging. MATERIALS AND METHODS: This is a retrospective, multicenter study. One hundred and forty-three patients with pT1b-pT3N0M0 ccRCC were included. Pathology specimens from surgeries were centrally reviewed, mounted on a tissue micro-array and stained with six markers: CAIX, c-MYC, Ki67, p53, vimentin and PTEN. Images were captured through an Ultra Fast Scanner. Tumor expression was measured with Image Pro Plus. Cytoplasmic markers (PTEN, CAIX, vimentin, c-MYC) were expressed as surface percentage of expression. Nuclear markers (Ki67, p53) were expressed as number of cells/mm2. Clinical data and markers expression were compared with clinical outcomes. Each variable was included in the Cox proportional multivariate analyses if p < 0.10 on univariate analyses. Discrimination of the new marker was calculated with Harrell's concordance index. RESULTS: At median follow-up of 63 months (IQR 35.0-91.8), on multivariate analysis, CAIX under-expression and vimentin over-expression were associated with worse survival (recurrence, specific and overall survival). A categorical marker CAIX-/Vimentin+ with cutoff points for CAIX and vimentin of 30 and 50 %, respectively, was designed. The new CAIX-/Vimentin+ marker presented a good concordance and comparable calibration to the reference model. Limitations are the retrospective design, the need for external validation and the large study period. CONCLUSION: Using an automated technique of measurement, CAIX and vimentin are independent predictors of clinical outcomes in ccRCC.

Prediction of renal mass aggressiveness using clinical and radiographic features: a global, multicentre prospective study.

OBJECTIVE: To examine the ability of preoperative clinical characteristics to predict histological features of renal masses (RMs). PATIENTS AND METHODS: Data from consecutive patients with clinical stage I RMs treated surgically between 2010 and 2011 in the Clinical Research Office of Endourology Society (CROES) Renal Mass Registry were collected. Based on surgical histology, tumours were categorised as benign, low- or high-aggressiveness cancer. Multivariate logistic regression was used to estimate the probability of the histological group by clinical and radiographic features in the entire cohort and a subcohort of cT1a tumours. The performance of the models was studied by calibration, Nagelkerke's R(2) , and discrimination (area under the receiver operating characteristic curve). RESULTS: The study cohort included 2 224 patients with a clinical stage I RM, of which 1 367 (61%) were cT1a. Benign lesions were found in 369 (16.6%), low-aggressiveness tumours in 1 156 (52%) and high-aggressiveness tumours in 699 (31.4%). Male gender, smoking history, increased tumour size, and lower exophytic rate were associated with malignancy and high-aggressiveness features (all P < 0.05). Models developed based on these characteristics had the ability to discriminate benign from malignant (bootstrap corrected c-index of 0.64) and high-aggressiveness tumours from benign and low-aggressiveness tumours (bootstrap corrected c-index of 0.66). Similar results were achieved in the cT1a subgroup. The c-index of tumour diameter as a single predictor of malignancy and high-aggressiveness tumours in the entire cohort was 0.6 and 0.63, respectively. CONCLUSION: Although older age, male gender, smoking history, increased tumour diameter, and reduced exophytic rate are associated with malignancy and high aggressiveness of clinical stage I RMs, models incorporating these characteristics have modest discriminating power, being only slightly better than the predictive ability of tumour size alone.