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Clear cell renal cell carcinoma (cc RCC) is the most prevalent adult kidney cancer. Prognostic markers are needed to guide patient management toward aggressive versus more conservative approaches, especially for small tumors ≤4 cm. miR-194 was reported to be downregulated in several cancers and is involved in epithelial to mesenchymal transition. We evaluated miR-194 as a prognostic marker in cc RCC. In a cohort of 234 patients with primary cc RCC, we correlated miR-194 expression level with multiple clinicopathological features including disease-free and overall survival, tumor size, clinical stage, and histological grade. Our results shows a stepwise decrease in miR-194 expression from normal kidney to primary cc RCC ( P = 0.0032) and a subsequent decrease from primary to metastatic lesions. Additionally, patients with higher miR-194 expression has significantly longer disease-free survival ( P = 0.041) and overall survival ( P = 0.031) compared to those with lower expression. In multivariate analysis, miR-194-positive tumors retain significance in disease-free survival and overall survival, suggesting miR-194 is an independent marker for good prognosis in cc RCC. Moreover, miR-194 is a marker for good prognosis for patients with small renal masses ( P = 0.014). These findings were validated on an independent data set from The Cancer Genome Atlas. We also compared miR-194 expression between RCC subtypes. cc RCC had the highest levels, whereas chromophobe RCC and oncocytoma had comparable lower levels. Target prediction coupled with pathway analysis show that miR-194 is predicted to target key molecules and pathways involved in RCC progression. miR-194 represents a prognostic biomarker in cc RCC. [ABSTRACT FROM AUTHOR]

Most reports of active surveillance (AS) of small renal masses (SRMs) lack biopsy confirmation, and therefore include benign tumors and different subtypes of renal cell carcinoma (RCC). We compared the growth rates and progression of different histologic subtypes of RCC SRMs (SRMRCC) in the largest cohort of patients with biopsy-characterized SRMs on AS. Data from patients in a multicenter Canadian trial and a Princess Margaret cohort were combined to include 136 biopsy-proven SRMRCC lesions managed by AS, with treatment deferred until progression or patient/surgeon decision. Growth curves were estimated from serial tumor size measures. Tumor progression was defined by sustained size ≥4 cm or volume doubling within 1 yr. Median follow-up for patients who remained on AS was 5.8 yr (interquartile range 3.4–7.5 yr). Clear cell RCC SRMs (SRMccRCC) grew faster than papillary type 1 SRMs (0.25 and 0.02 cm/yr on average, respectively, p = 0.0003). Overall, 60 SRMRCC lesions progressed: 49 (82%) by rapid growth (volume doubling), seven (12%) increasing to ≥4 cm, and four (6.7%) by both criteria. Six patients developed metastases, and all were of clear cell RCC histology. Limitations include the use of different imaging modalities and a lack of central imaging review. Tumor growth varies between histologic subtypes of SRMRCC and among SRMccRCC, which likely reflects individual host and tumor biology. Without validated biomarkers that predict this variation, initial follow-up of histologically characterized SRMs can inform personalized treatment for patients on AS. Many small kidney cancers are suitable for surveillance and can be monitored over time for change. We demonstrate that different types of kidney cancers grow at different rates and are at different risks of progression. These results may guide better personalized treatment. Tumor growth varies within and between histological subtypes of small renal masses (renal cell carcinomas), which likely reflects individual host and tumor biology. Histology-specific growth rates and initial monitoring of small renal masses can inform personalized treatment for patients on active surveillance. [ABSTRACT FROM AUTHOR]

Abstract: The use of needle biopsies in basic research is increasing, and our study provides a comprehensive analysis of their adequacy in genomic and proteomic studies of kidney cancer. Frozen clear cell renal cell carcinoma (ccRCC) needle core biopsies and sections from core biopsies embedded in optimal cutting temperature (OCT) compound were used to extract DNA, RNA and protein. Their integrity was determined using genomic and proteomic analyses. VHL mutation testing was performed on ccRCC biopsies and corresponding tumors using bulk and laser capture microdissection (LCM) extractions for comparison. Adequate amounts of good quality DNA (5.8–13.3μg/whole core, 0.6–2.7μg/20 sections), RNA (2.9–11.9μg/whole core, 0.5–1.3μg/20 sections) and protein (137.4–444μg/whole core, 39.9–74.1μg/20 sections) were obtained from whole core and frozen sections of ccRCC needle biopsies, respectively. We observed VHL sequence mutations in 75% of ccRCC tumors and, in most cases, the same mutations were detected in both tumors and corresponding biopsies. Mutations observed by bulk extractions from tumors and biopsies were also detected by LCM without significant differences between both methodologies. ccRCC needle biopsies provide ample material for genomic and proteomic studies of kidney cancer. They are good representatives of their corresponding tumors for VHL mutation detection using both bulk and LCM extractions. LCM does not increase sensitivity of VHL mutation detection. [Copyright &y& Elsevier]

Abstract: Background: Most early stage kidney cancers are renal cell carcinomas (RCCs), and most are diagnosed incidentally by imaging as small renal masses (SRMs). Indirect evidence suggests that most small RCCs grow slowly and rarely metastasize. Objective: To determine the progression and growth rates for newly diagnosed SRMs stratified by needle core biopsy pathology. Design, setting, and participants: A multicenter prospective phase 2 clinical trial of active surveillance of 209 SRMs in 178 elderly and/or infirm patients was conducted from 2004 until 2009 with treatment delayed until progression. Intervention: Patients underwent serial imaging and needle core biopsies. Measurements: We measured rates of change in tumor diameter (growth measured by imaging) and progression to ≥4cm, doubling of tumor volume, or metastasis with histology on biopsy. Results and limitations: Local progression occurred in 25 patients (12%), plus 2 progressed with metastases (1.1%). Of the 178 subjects with 209 SRMs, 127 with 151 SRMs had>12 mo of follow-up with two or more images, with a mean follow-up of 28 mo. Their tumor diameters increased by an average of 0.13cm/yr. Needle core biopsy in 101 SRMs demonstrated that the presence of RCC did not significantly change growth rate. Limitations included no central review of imaging and pathology and a short follow-up. Conclusions: This is the first SRM active surveillance study to correlate growth with histology prospectively. In the first 2 yr, the rate of local progression to higher stage is low, and metastases are rare. SRMs appear to grow very slowly, even if biopsy proven to be RCC. Many patients with SRMs can therefore be initially managed conservatively with serial imaging, avoiding the morbidity of surgical or ablative treatment. [Copyright &y& Elsevier]

Abstract: Background: Renal cell carcinoma (RCC) encompasses different histologic subtypes. Distinguishing between the subtypes is usually made by morphologic assessment, which is not always accurate. Objective: Our aim was to identify microRNA (miRNA) signatures that can distinguish the different RCC subtypes accurately. Design, setting, and participants: A total of 94 different subtype cases were analysed. miRNA microarray analysis was performed on fresh frozen tissues of three common RCC subtypes (clear cell, chromophobe, and papillary) and on oncocytoma. Results were validated on the original as well as on an independent set of tumours, using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis with miRNA-specific primers. Measurements: Microarray data were analysed by standard approaches. Relative expression for qRT-PCR was determined using the ΔΔCT method, and expression values were normalised to small nucleolar RNA, C/D box 44 (SNORD44, formerly RNU44). Experiments were done in triplicate, and an average was calculated. Fold change was expressed as a log2 value. The top-scoring pairs classifier identified operational decision rules for distinguishing between different RCC subtypes and was robust under cross-validation. Results and limitations: We developed a classification system that can distinguish the different RCC subtypes using unique miRNA signatures in a maximum of four steps. The system has a sensitivity of 97% in distinguishing normal from RCC, 100% for clear cell RCC (ccRCC) subtype, 97% for papillary RCC (pRCC) subtype, and 100% accuracy in distinguishing oncocytoma from chromophobe RCC (chRCC) subtype. This system was cross-validated and showed an accuracy of about 90%. The oncogenesis of ccRCC is more closely related to pRCC, whereas chRCC is comparable with oncocytoma. We also developed a binary classification system that can distinguish between two individual subtypes. Conclusions: MiRNA expression patterns can distinguish between RCC subtypes. [Copyright &y& Elsevier]