scholarly journals MicroRNAs as Urinary Biomarker for Oncocytoma

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Melanie von Brandenstein ◽  
Monika Schlosser ◽  
Jan Herden ◽  
Axel Heidenreich ◽  
Stefan Störkel ◽  
...  

The identification of benign renal oncocytoma, its differentiation from malignant renal tumors, and their eosinophilic variants are a continuous challenge, influencing preoperative planning and being an unnecessary stress factor for patients. Regressive changes enhance the diagnostic dilemma, making evaluations by frozen sections or by immunohistology (on biopsies) unreliable. MicroRNAs (miRs) have been proposed as novel biomarkers to differentiate renal tumor subtypes. However, their value as a diagnostic biomarker of oncocytoma in urines based on mechanisms known in oncocytomas has not been exploited. We used urines from patients with renal tumors (oncocytoma, renal cell carcinoma: clear cell, papillary, chromophobe) and with other urogenital lesions. miRs were extracted and detected via qRT-PCR, the respective tumors analyzed by immunohistology. We found isocitrate dehydrogenase 2 upregulated in oncocytoma and oncocytic chromophobe carcinoma, indicating an increased Krebs cycle metabolism. Since we had shown that all renal tumors are stimulated by endothelin-1, we analyzed miRs preidentified by microarray after endothelin-1 stimulation of renal epithelial cells. Four miRs are proposed as presurgical urinary biomarkers due to their known regulatory mechanism in oncocytoma: miR-498 (formation of the oncocytoma-specific slice-form of vimentin, Vim3), miR-183 (associated with increased CO2 levels), miR-205, and miR-31 (signaling through downregulation of PKC epsilon, shown previously).

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 408-408 ◽  
Author(s):  
L. Albiges ◽  
J. Couturier ◽  
Y. Allory ◽  
P. Camparo ◽  
M. Sibony ◽  
...  

408 Background: Chromophobe renal cell carcinoma (chRCC) and renal oncocytoma (Onc) are two distinct but closely related entities with strong morphologic and genetic similarities. While chRCC is a malignant tumor, Onc is usually considered as a benign entity. Recently, gene expression profiling applied on chRCC and Onc identified new potential markers that may effectively discriminate the 2 pathologic entities, including parafibromin. This work aims at evaluating the diagnostic value of Parafibromin (Pf) immuno staining on a large number of renal tumor samples. Methods: Sixty-three renal clear cell carcinoma (ccRCC), 47 papillary (Pap), 40 chRCC, and 75 Onc were immunostained for parafibromin antibody (1/200; Santacruz Biotechnology), on a tissue micro array. Results: Parafibromin was positive in 38.6% of Onc, vs 5% of chRCC (p < 0.001), with a 95% specificity, and the positive predictive value observed for parafibromin was 94%. For other tumor types, a positive staining for parafibromin was observed in 7.9% and 8.5% in ccRCC and Pap respectively. Conclusions: Parafibromin is a recently identified protein which seems to be specific for oncocytoma, and highly discriminant for other histologic renal cell tumor subtypes, especially for chromophobe. IHC may help to optimize therapeutics strategy for small renal mass and avoid surgical resection of benign lesions in some patients.Validation of this staining on renal tumor biopsies is on going.The value of the combination of this new immunostaining associated with the three standard IHC staining (CK7, CD117, E Cad) will be provided at the meeting. [Table: see text] No significant financial relationships to disclose.


2019 ◽  
Vol 45 (10) ◽  
pp. 3193-3201 ◽  
Author(s):  
Yajuan Li ◽  
Xialing Huang ◽  
Yuwei Xia ◽  
Liling Long

Abstract Purpose To explore the value of CT-enhanced quantitative features combined with machine learning for differential diagnosis of renal chromophobe cell carcinoma (chRCC) and renal oncocytoma (RO). Methods Sixty-one cases of renal tumors (chRCC = 44; RO = 17) that were pathologically confirmed at our hospital between 2008 and 2018 were retrospectively analyzed. All patients had undergone preoperative enhanced CT scans including the corticomedullary (CMP), nephrographic (NP), and excretory phases (EP) of contrast enhancement. Volumes of interest (VOIs), including lesions on the images, were manually delineated using the RadCloud platform. A LASSO regression algorithm was used to screen the image features extracted from all VOIs. Five machine learning classifications were trained to distinguish chRCC from RO by using a fivefold cross-validation strategy. The performance of the classifier was mainly evaluated by areas under the receiver operating characteristic (ROC) curve and accuracy. Results In total, 1029 features were extracted from CMP, NP, and EP. The LASSO regression algorithm was used to screen out the four, four, and six best features, respectively, and eight features were selected when CMP and NP were combined. All five classifiers had good diagnostic performance, with area under the curve (AUC) values greater than 0.850, and support vector machine (SVM) classifier showed a diagnostic accuracy of 0.945 (AUC 0.964 ± 0.054; sensitivity 0.999; specificity 0.800), showing the best performance. Conclusions Accurate preoperative differential diagnosis of chRCC and RO can be facilitated by a combination of CT-enhanced quantitative features and machine learning.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jianxiong Fu ◽  
Jing Ye ◽  
Wenrong Zhu ◽  
Jingtao Wu ◽  
Wenxin Chen ◽  
...  

Abstract Background Benign and malignant renal tumors share similar some imaging findings. Methods Sixty-six patients with clear cell renal cell carcinoma (CCRCC), 13 patients with renal angiomyolipoma with minimal fat (RAMF) and 7 patients with renal oncocytoma (RO) were examined. For diffusion kurtosis imaging (DKI), respiratory triggered echo-planar imaging sequences were acquired in axial plane (3 b-values: 0, 500, 1000s/mm2). Mean Diffusivity (MD), fractional Anisotropy (FA), mean kurtosis (MK), kurtosis anisotropy (KA) and radial kurtosis (RK) were performed. Results For MD, a significant higher value was shown in CCRCC (3.08 ± 0.23) than the rest renal tumors (2.93 ± 0.30 for RO, 1.52 ± 0.24 for AML, P < 0.05). The MD values were higher for RO than for AML (2.93 ± 0.30 vs.1.52 ± 0.24, P < 0.05), while comparable MD values were found between CCRCC and RO (3.08 ± 0.23 vs. 2.93 ± 0.30, P > 0.05). For MK, KA and RK, a significant higher value was shown in AML (1.32 ± 0.16, 1.42 ± 0.23, 1.41 ± 0.29) than CCRCC (0.43 ± 0.08, 0.57 ± 0.16, 0.37 ± 0.11) and RO (0.81 ± 0.08, 0.86 ± 0.16, 0.69 ± 0.08) (P < 0.05). The MK, KA and RK values were higher for RO than for CCRCC (0.81 ± 0.08 vs. 0.43 ± 0.08, 0.86 ± 0.16 vs. 0.57 ± 0.16, 0.69 ± 0.08 vs. 0.37 ± 0.11, P < 0.05). Using MD values of 2.86 as the threshold value for differentiating CCRCC from RO and AML, the best result obtained had a sensitivity of 76.1%, specificity of 72.6%. Using MK, KA and RK values of 1.19,1.13 and 1.11 as the threshold value for differentiating AML from CCRCC and RO, the best result obtained had a sensitivity of 91.2, 86.7, 82.1%, and specificity of 86.7, 83.2, 72.8%. Conclusion DKI can be used as another noninvasive biomarker for benign and malignant renal tumors’ differential diagnosis.


2007 ◽  
Vol 131 (10) ◽  
pp. 1541-1546 ◽  
Author(s):  
Christopher D. Hornsby ◽  
Cynthia Cohen ◽  
Mahul B. Amin ◽  
Maria M. Picken ◽  
Diane Lawson ◽  
...  

Abstract Context.—The differential diagnosis of eosinophilic renal tumors can be difficult by light microscopy. In particular, chromophobe renal cell carcinoma (RCC) is difficult to distinguish from oncocytoma. This differential diagnosis is important because chromophobe RCC is malignant, whereas oncocytoma is benign. Furthermore, chromophobe RCC has distinct malignant potential and prognosis compared with eosinophilic variants of other RCC subtypes. Immunohistochemistry is useful for distinguishing chromophobe RCC from other subtypes of renal carcinoma, but no expression marker reliably separates chromophobe RCC from oncocytoma. Objective.—In a previous gene expression microarray analysis of renal tumor subtypes, we found the distal nephron markers claudin-7 and claudin-8 to be overexpressed in chromophobe RCC versus oncocytoma and other tumor subtypes. We have confirmed similar findings in independent microarray data and validated differential claudin-7 protein expression by immunohistochemistry. Design.—Immunohistochemical analysis of claudin-7 in 36 chromophobe RCCs, 43 oncocytomas, 42 clear cell RCCs, and 29 papillary RCCs. Results.—Membranous claudin-7 expression was detected in 67% chromophobe RCCs, compared with 0% clear cell RCCs, 28% papillary RCCs, and 26% oncocytomas (P &lt; .001). Conclusions.—Based on microarray and immunohistochemical data, we propose claudin-7 to be a candidate expression marker for distinguishing chromophobe RCC from other renal tumor subtypes, including the morphologically similar oncocytoma. The clinical utility of claudin-7 should be validated in independent studies of renal tumors, possibly in combination with additional targets in a multiplex immunohistochemical panel.


2007 ◽  
Vol 131 (12) ◽  
pp. 1782-1788 ◽  
Author(s):  
Ondrej Hes ◽  
Michal Michal ◽  
Naoto Kuroda ◽  
Guido Martignoni ◽  
Matteo Brunelli ◽  
...  

Abstract Context.—The expression of vimentin in benign renal oncocytomas has been controversal. However, this is of clinical significance because immunostains may be used in differential diagnosis of renal tumors on limited biopsy specimens. Using different staining and analysis methods, we studied vimentin immunoreactivity in a large series of renal oncocytomas with a special emphasis on the immunoreactivity patterns. Objective.—Immunohistochemical expression of vimentin has been used in the differential diagnosis of renal epithelial neoplasms. Although typically expressed in most renal cell carcinomas, the immunoreactivity of this intermediate filament in renal oncocytomas has been controversial. Design.—We studied vimentin immunoreactivity in a large series of 234 renal oncocytomas using 2 staining methods as well as manual and automated imaging analyses. Results.—We found that the focal vimentin immunoreactivity can be seen in most (72.6%) renal oncocytomas with vimentin-positive tumor cells usually found in the edge of a central scar or in small clusters scattered throughout the tumor. Computer-aided imaging analysis using ChromaVision Automatic Cellular Imaging System II confirmed the difference in vimentin immunoreactivity between oncocytoma and other renal neoplasms. Conclusions.—Our study of vimentin immunohistochemistry in a series of renal oncocytomas, which to our knowledge is the largest ever published, showed focal vimentin positivity detected in most oncocytomas. Because the vimentin staining patterns in renal oncocytomas are different from those seen in clear cell or papillary renal cell carcinomas, we consider vimentin staining to be helpful in the differential diagnosis of oncocytoma from other renal tumor mimics. Furthermore, strong vimentin positivity in a renal cell neoplasm does not exclude the diagnosis of renal oncocytoma, particularly in a limited biopsy specimen.


2009 ◽  
Vol 76 (2) ◽  
pp. 130-132
Author(s):  
M. Esposito ◽  
V. Varca ◽  
A. Simonato ◽  
C. Toncini ◽  
G. Carmignani ◽  
...  

The coexistence of multiple, synchronous primary tumors of different histology within the same kidney is a rare condition. We report herein a series of five patients with two tumors of different histology involving synchronously the same kidney. Materials and Methods We reviewed the pathology reports of a series of 381 patients who underwent surgery for primary renal tumors at our institution from 2000 to 2007. In the files of all patients with synchronous tumors of different histology, special attention was given to the results of imaging studies. Results Five out of 381 patients (1.37%) had coexistence of two primary tumors of different histology within the same kidney. Four patients had ultrasonography as the first imaging procedure, one patient had ultrasonography as the second imaging procedure; all had preoperative CT of the abdomen. Both lesions were detected by preoperative CT in 4/5 of the cases; in the remaining one, the smaller lesion was not visible, even in retrospect. Conclusions The coexistence of multiple and synchronous primary tumors of different histology within the same kidney has been only rarely described. To the best of our knowledge, in literature there are only case reports with the exception of a case of renal oncocytoma with evolving papillary RCC. We believe that this condition could be more frequent if the radiologist and the anatomopathologist try to find it.


2017 ◽  
Vol 84 (4) ◽  
pp. 244-250
Author(s):  
Michele Scialpi ◽  
Eugenio Martorana ◽  
Valeria Rondoni ◽  
Ahmed Eissa ◽  
Ahmed El Sherbiny ◽  
...  

Introduction Although differentiation between benign and malignant small renal tumors (≤4 cm) is still difficult, it is a demand for decision making and determining the treatment strategy. Our aim is to evaluate the role of multidetector row computed tomography (MDCT) in the differentiation of small renal clear cell carcinoma (RCC) and renal oncocytoma (RO). Methods We reviewed triphasic computed tomographic (CT) scans performed in 43 patients diagnosed with RCC (n = 23) and RO (n = 21). After an unenhanced CT phase of the upper abdomen, triple-phase acquisition included a cortico-medullary phase (CMP), a nephrographic phase (NP), and a pyelographic phase (PP), and lesions were evaluated both qualitatively and quantitatively. Results RCCs were hypervascular in 13 cases and hypovascular in 10 cases, while ROs were hypervascular in nine cases and hypovascular in 12 cases. Mean attenuation values (MAVs) for hypervascular RCCs and hypervascular ROs on unenhanced examination were 34.0 ± 7.1 and 31.3 ± 8.1 HU, respectively. Enhancement in CMP was 173.1 ± 45.2 HU for RCCs and 151.1 ± 36.0 HU for ROs and a gradual wash-out in NP (148.8 ± 34.3 and 137.1 ± 33.9 HU for RCCs and ROs, respectively) and in PP (98.2 ± 36.0 HU for RCCs and 79.4 ± 21.5 HU for ROs) was observed. MAV for hypovascular RCCs and hypovascular ROs on unenhanced examination were 32.4 ± 12.0 and 28.9 ± 8.0 HU, respectively. Both hypovascular RCCs and ROs showed a statistically significant difference in each post contrastographic phase. Conclusions Absolute attenuation and the quantitative amount of the enhancement were not strong predictors for RO and RCC differentiation.


Heart ◽  
2014 ◽  
Vol 100 (Suppl 3) ◽  
pp. A114-A114 ◽  
Author(s):  
Andrew Vanezis ◽  
Chokanan Thaitirarot ◽  
Madiha Butt ◽  
Iain Squire ◽  
Nilesh Samani ◽  
...  

2012 ◽  
Vol 2012 ◽  
pp. 1-3 ◽  
Author(s):  
Adam J. Horn ◽  
Bari E. Fritz ◽  
Chad A. LaGrange ◽  
William W. West ◽  
Subodh M. Lele

Tumors-to-tumor metastasis is an uncommon occurrence and can be a source of great diagnostic difficulty, especially when the donor tumor is undiagnosed. Here we report a case of a kidney resected for a primary neoplasm (oncocytoma) that harbored metastases from a clinically undiagnosed prostatic adenocarcinoma. The presence of the poorly differentiated metastasis within an otherwise typical oncocytoma in the absence of metastases in the surrounding nonneoplastic renal parenchyma resulted in a diagnostic dilemma. To our knowledge, this is the first report of a case in the English literature of a clinically undiagnosed prostatic adenocarcinoma metastatic to a renal oncocytoma identified on examination of the resected renal neoplasm.


2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Katarína Smolková ◽  
Petr Ježek

Isocitrate dehydrogenase 2 (IDH2) is located in the mitochondrial matrix. IDH2 acts in the forward Krebs cycle as an NADP+-consuming enzyme, providing NADPH for maintenance of the reduced glutathione and peroxiredoxin systems and for self-maintenance by reactivation of cystine-inactivated IDH2 by glutaredoxin 2. In highly respiring cells, the resulting NAD+accumulation then induces sirtuin-3-mediated activating IDH2 deacetylation, thus increasing its protective function. Reductive carboxylation of 2-oxoglutarate by IDH2 (in the reverse Krebs cycle direction), which consumes NADPH, may follow glutaminolysis of glutamine to 2-oxoglutarate in cancer cells. When the reverse aconitase reaction and citrate efflux are added, this overall “anoxic” glutaminolysis mode may help highly malignant tumors survive aglycemia during hypoxia. Intermittent glycolysis would hypothetically be required to provide ATP. When oxidative phosphorylation is dormant, this mode causes substantial oxidative stress. Arg172 mutants of human IDH2—frequently found with similar mutants of cytosolic IDH1 in grade 2 and 3 gliomas, secondary glioblastomas, and acute myeloid leukemia—catalyze reductive carboxylation of 2-oxoglutarate and reduction toD-2-hydroxyglutarate, which strengthens the neoplastic phenotype by competitive inhibition of histone demethylation and 5-methylcytosine hydroxylation, leading to genome-wide histone and DNA methylation alternations.D-2-hydroxyglutarate also interferes with proline hydroxylation and thus may stabilize hypoxia-induced factorα.


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