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Objective: Our aim was to evaluate the performance of fine needle aspiration (FNA) as a method for obtaining cellular material for the tissue diagnosis of small solid renal tumours., Methods: Fifty-five patients with a small solid renal tumour (4 cm or smaller) underwent a FNA biopsy under computed tomography guidance. Direct smears and rinse of needle with Cytolyt® were prepared. The cellular adequacy was divided into three groups: satisfactory cellular material, scant cellular material and noncellular material., Results: Postoperative pathological diagnosis showed 35 clear cell carcinomas, 10 papillary carcinomas, four chromophobe carcinomas, four oncocytomas, one adenoma and one metastatic carcinoma. A total of 21 (38.2%) FNA biopsies belonged to noncellular group. For clear cell carcinomas, the cellularity of satisfactory cellular group, scant cellular group and noncellular group was, respectively, seven (20.0%), nine (25.7%) and 19 (54.3%). Of the 10 papillary carcinomas, nine (90%) and all four chromophobe carcinomas (100%) had satisfactory cellular materials. The percentages of noncellular group among clear cell carcinoma, papillary carcinoma and chromophobe carcinoma were significantly different (P = 0.0020). Fifteen tumours were 2 cm or smaller and 40 tumours were larger than 2 cm. No significant difference was found in the percentage of noncellular material for the tumours 2 cm or less (40.0%) and for the tumours larger than 2 cm (37.5%; P > 0.05)., Conclusions: The cellularity of FNA biopsy of small solid renal masses might correlate with the subtype of renal cancers. FNA biopsy was an effective method of tissue sampling for papillary and chromophobe renal carcinomas., (© 2018 John Wiley & Sons Ltd.)

Background: Recent findings show that cell-free miRNAs are stable in biological fluid. Urine provides an alternative to blood serum or plasma as a potential source of tumor biomarkers. MiR-210 is proven to be overexpressed in patients with a clear cell renal cell carcinoma (ccRCC). The purpose of this pilot study was to examine the urinary cell-free miR-210 as a potential tool of liquid biopsy for ccRCC., Methods: Overall, 75 patients with a ccRCC and 45 control subjects without a cancer were included in this study. Urine samples were centrifuged twice and the cell-free urine supernanants were stored in -80°C until use. A total of 350µl cell-free urine was used for the extraction of total RNA. The expression levels of these miRNAs were performed by using quantitative RT-PCR., Results: The level of urinary cell-free miR-210 was significantly higher in patients with ccRCC than in control subjects (P<0.001). The urinary cell-free miR-210 yielded the areas under the receiver operating characteristics curve of 0.76 in discriminating the patients with ccRCC from the control subjects with a sensitivity of 57.8% and a specificity of 80.0%. Moreover, the expression level of urinary cell-free miRNA-210 was significantly decreased in the patients a week after surgery (P<0.001)., Conclusion: Urinary cell-free miR-210 may be used as a potential tool of liquid biopsy for ccRCC diagnosis. Further studies are needed to confirm our results., (Copyright © 2017. Published by Elsevier Inc.)

Purpose: The purpose of our study was to test the utility of CA9 expression in preoperative biopsy samples to identify the ccRCC., Materials and Methods: A total of 55 patients with a small solid renal mass (≤4 cm) entered into this study. The immunohistochemical staining (51 samples) and RT-PCR (33 samples) were performed to detect CA9 expression., Results: For immunohistochemistry detection, CA9 was positive in 31/34 of biopsy samples of ccRCCs. CA9 was also positive in five suspected diagnosis of ccRCC. For RT-PCR detection, CA9 was positive in 25/25 biopsy samples of ccRCCs. The diagnostic accuracy of CA9 expression for ccRCC was 100%. RT-PCR was performed in four biopsies where immunohistochemistry could not be performed because of limited tissue materials or necrosis. Two ccRCCs with a negative staining by immunohistochemistry were CA9 positive by RT-PCR., Conclusions: CA9 may be potentially useful biomarker in help making a diagnosis of ccRCC in the biopsy of renal mass. RT-PCR might be a preferred method to immunohistochemistry for the detection of CA9 in renal biopsy samples.

There is limited research on cell-free RNA (cf-RNA) in the urine of cancer patients. The present study was performed to detect the cf-RNA in the urine of patients with clear cell renal cell carcinoma (ccRCC). Ninety-five urine samples from ccRCC patients and 50 urine samples from control subjects were analyzed. The cf-RNA integrity index was calculated by using quantitative real-time RT-PCR assays of the small-sized fragment (106 bp) and the big-sized fragment (416 bp) in GAPDH mRNA. The initial analysis showed that cf-RNA was stable and detectable in the urine. The mean cf-RNA integrity index was significantly lower in the urine of ccRCC patients (mean: 0.07, 95%CI: 0.05-0.10) when compared with the urine from control subjects (mean: 0.25, 95%CI: 0.16-0.33) (p < 0.001). The value of the area under the receiver-operating characteristic curve by using the cf-RNA integrity index for the diagnosis of ccRCC was 0.858 with a sensitivity of 68.0% and a specificity of 92.6%. Moreover, the small-sized VEGF mRNA fragment (98 bp) was detected in 31 of 50 urine samples of patients with ccRCC and in only 2 of 50 urine samples of control subjects (p < 0.001) while the detection of the big-sized (420 bp) VEGF mRNA fragment was an infrequent event. Our findings suggest that the small-sized cf-RNA in urine was more abundant in cancer patients. The tumor-related gene VEGF mRNA fragment was detectable in the urine of cancer patients. Our finding may provide a new molecular assay for the diagnosis of renal cell carcinoma., (© 2014 UICC.)

Introduction: A disintegrin and metalloproteinase-17 (ADAM17) plays an important role in biological activity in different cancers. Its expression and prognostic value have not been studied in clear cell renal cell carcinoma (cRCC). The objective of this study was to explore the prognostic value of ADAM17 in patients with cRCC., Materials and Methods: A total of 131 patients with cRCC were studied. There were 90 men and 41 women, with an average age of 67 years (range: 34-93 y). There were 110 patients with localized disease and 21 patients with metastatic disease. The expression of ADAM17 was evaluated by immunohistochemistry with a monoclonal antibody. The follow-up varied from 4.2 to 184 months, with a median of 72 months for patients with localized disease. Kaplan-Meier with a log-rank test was performed to compare the progression-free survival after surgery. The univariate and multivariate analyses were performed to examine the significance of ADAM17 expression for the patient's progression-free survival., Results: The ADAM17 expression was found in 109/131 tumors. The ADAM17 expression was found in 20/21 metastatic tumors and in 89/110 localized tumors. Regarding patients with localized tumors, 31 patients experienced a recurrence or death during follow-up. The Kaplan-Meier analysis revealed that the high expression of ADAM17 was associated with a reduced progression-free survival (P = 0.005). The univariate logistic regression analysis indicated that the high expression of ADAM17 was associated with the disease progression (hazard ratio = 2.826; 95% CI: 1.324-6.034; P = 0.007). The high expression of ADAM17 remained a significant factor for decreased progression-free survival in multivariate analysis., Conclusion: ADAM17 was frequently expressed in cRCC. The high expression of ADAM17 was correlated with a worse outcome for patients with cRCC. ADAM17 is a new biomarker for the management of patients with cRCC., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To report on a series of fine needle aspiration (FNA) biopsies for preoperative diagnosis of complex cystic renal mass., Study Design: From August 2002 to February 2009, 32 patients with a complex cystic renal mass were studied. Tumor size ranged from 1.5-7.7 cm, with a median of 3.0 cm. Bosniak classification was 15 IIF, 12 III, and 5 IV. FNA biopsy was performed under CT guidance to obtain the fluid. Malignant and suspect cytological reports were considered as a positive diagnosis, and absence of epithelial cells as a negative diagnosis., Results: Sufficient fluid was obtained in all cases. A positive preoperative diagnosis was found in 11 patients, and 21 cysts presented as absence of epithelial cells. Of the 26 patients who underwent surgery, pathology proved that there were 21 malignant and 5 benign cysts. Among the operated patients with a malignant cystic tumor, 11/21 (52.3%) presented a negative preoperative diagnosis. One preoperative positive diagnosis was proved to be a benign cyst. The accuracy of preoperative positive cytology was 10/11 (90.9%)., Conclusion: No difficulty was noticed in obtaining the fluid by FNA of a cystic small renal mass. A false negative diagnosis was due mainly to the absence of malignant cells in the fluid of cysts. Biomarkers in fluid shall be studied to solve the diagnostic problem.

Objectives: The common subtypes of renal tumors are conventional or clear cell carcinoma, papillary carcinoma, chromophobe carcinoma and oncocytoma. Each subtype has its distinct histogenesis and clinical evolution. DNA ploidy is viewed as a marker of gross genomic aberrations. The aim of this study is to evaluate the DNA ploidy in the common subtypes of renal tumors to increase our understanding of renal tumor biology and to broaden clinical application of DNA ploidy., Methods: 38 renal tumor samples (13 clear cell RCCs, 12 papillary RCCs, 7 chromophobe RCCs, and 6 oncocytomas) were studied. Five biopsies of different parts of each fresh tumor were subjected to a flow cytometric analysis of DNA ploidy., Results: All tumors except one papillary RCC generated interpretable DNA histograms. Flow cytometric analysis of oncocytomas showed the diploid pattern (29/30 frequencies) while the chromophobe RCC never showed the diploid pattern (0/55 frequencies) (p<0.01). 3/7 chromopbobe RCCs possessed the hypodiploid stemline. The hypodiploid stemline appeared neither in conventional RCCs (0/63 frequencies) nor in papillary RCCs (0/50 frequencies). The diploid pattern was dominant in conventional and papillary RCCs. 10/13 (76.9%) of clear cell RCCs and 9/11 (81.8%) of papillary RCCs possessed a homogeneous DNA ploidy pattern while only 1/7 (14.3%) has a homogeneous DNA ploidy pattern. 6/7 chromophobe RCCs had multiple aneuploid stemlines., Conclusions: Flow cytometric analysis reveals that conventional and papillary RCCs are more homogeneous than chromophobe RCC. Each subtype of renal tumors possesses a specific DNA ploidy pattern. The analysis of DNA ploidy is useful for the differentiation of common subtypes of renal tumors in morphologically difficult cases.

Purpose: The aim of this study was to develop a practical technique to detect mRNA expression and to validate a panel of mRNA markers for molecular differential diagnosis of renal cell carcinoma (RCC)., Experimental Design: The renal cancer cell line SKRC-52 was used to set up the technique, which consisted of column extraction of RNA and one-step reverse transcription-PCR. We validated a panel of gene markers, including MN/CA9, cadherin-6, vimentin, mucin1, and parvalbumin, and studied 50 renal tumors (30 conventional, 9 papillary, and 5 chromophobe RCCs and 6 oncocytomas), 10 normal tissues, and 10 normal blood samples. We mimicked fine needle aspiration (FNA) biopsy in 10 kidneys with conventional RCC and applied this technique to 10 preoperative FNA samples from imaging-indeterminate renal tumors., Results: The technique could detect as few as 10 SKRC-52 cells with MN/CA9 as mRNA marker and was less time consuming and labor intensive. MN/CA9 was a sensitive and rather specific gene marker for conventional RCC. Cadherin-6 gene expression was a sensitive marker for conventional and papillary RCC. Vimentin was highly specific for conventional RCC. Mucin1 mRNA was sensitive for papillary and chromophobe RCC and oncocytoma. Parvalbumin mRNA was a sensitive and highly specific marker for both chromophobe RCC and oncocytoma. Thus, these mRNA markers represent the biomarker genes for the subtypes of renal tumors. Finally, we successfully applied the technique to FNA specimens. Five preoperative FNA samples were MN/CA9 gene positive, suggesting a RCC, whereas the routine cytology was positive in only three cases., Conclusions: A rapid and sensitive assay of mRNA markers was developed for molecular differential diagnosis of RCC. This molecular assay can be used as a powerful ancillary to surgical pathological diagnosis and cytological diagnosis of RCC.

Although numerous studies on the prognostic value of DNA aneuploidy in RCC have been reported, the in vivo DNA aneuploidization during RCC expansion has not been revealed. The present study was undertaken to observe the DNA aneuploidization during RCC expansion. We studied prospectively 67 consecutive conventional RCCs. The ploidy status was determined by analyzing five fresh tumor tissues from different areas by flow cytometry. The diploid, heterogeneous aneuploid tumors and homogeneous aneuploid tumors could be detected, respectively, in 44.8%, 23.9% and 31.3% of cases. The diploid tumors decreased significantly and aneuploid tumors increased significantly as the tumor expanded. The similar DNA content distribution was found between the heterogeneous aneuploid tumors and homogeneous aneuploid tumors. The hypertriploid clone was the most frequent in aneuploid tumors. The tumors of multiple aneuploid clones (16.4%) were mainly found in large-sized tumors. These results suggested that some RCCs underwent DNA aneuploidization during the tumor expansion and that a major route of aneuploidiztion (hypertriploidization) and several pathways existed. Our results also supported the idea that the progressive chromosomal instability was associated with continued tumor growth of RCC. The molecular mechanism and the clinical significance of aneuploidy phenotypes need to be further investigated.