scholarly journals Clinical Utility of Chromosome Genomic Array Testing for Unclassified and Advanced-Stage Renal Cell Carcinomas

2018 ◽  
Vol 143 (4) ◽  
pp. 494-504 ◽  
Author(s):  
Nicole K. Andeen ◽  
Xiaoyu Qu ◽  
Tatjana Antic ◽  
Scott S. Tykodi ◽  
Min Fang ◽  
...  

Context.— Cytogenomic analysis provides a useful adjunct to traditional pathology in the categorization of renal cell carcinomas (RCCs), particularly in morphologically ambiguous cases, but it has disadvantages, including cost. Objective.— To define the clinical scenarios in which this technology has direct clinical applications. Design.— DNA was isolated from paraffin-embedded tissue from 40 selected cases of RCC. Chromosome genomic array testing was performed using the OncoScan. Results.— Of 23 cases of unclassified renal tumors, 19 (83%) were reclassified with incorporation of cytogenetic and histologic features, including 10 as clear cell RCC, 2 as collecting duct carcinoma, 2 as papillary RCC, and 1 as novel TFEB-amplified tumor lacking TFEB translocation. Of 5 tumors with “hybrid” oncocytic features, 3 were reclassified as an eosinophilic variant of chromophobe RCC and 1 as oncocytoma. Appropriate staging in 2 patients was determined by identifying distinct, nonshared cytogenetic profiles. Of 11 cases of metastatic clear cell RCC, 7 (63%) had cytogenetic features associated with a poor prognosis. Conclusions.— We identified 5 scenarios in which chromosome genomic array testing has direct clinical utility: (1) to investigate unclassified RCCs, (2) to understand tumors with “hybrid” features and “collision” tumors, (3) to determine appropriate staging in questions of bilateral tumors and/or metastases, (4) to identify chromosomal aberrations in metastatic clear cell RCCs associated with a worse prognosis, and (5) to identify new entities. This has practical value in our institution, where a molecular profile diagnostically separating morphologically difficult to classify clear cell, papillary, chromophobe, and unclassified RCC influences treatment recommendations and clinical trial eligibility.

2019 ◽  
Vol 31 (4) ◽  
pp. 921-924
Author(s):  
Atanas Ivanov ◽  
Vili Stoyanova

Renal tumors account for about 3% of the malignancies in adults. Clear cell subtype renal cell carcinoma (RCC) and papillary RCC are the most common renal tubular epithelial carcinomas and their differentiation is important because they have a different prognosis and are associated with different treatment protocols. In most cases, histological features allow accurate diagnosis of renal cell carcinomas. There are also overlapping morphological findings between certain kidney neoplasms that make their subtyping extremely difficult. Some of them display papillary architecture but also have a clear cell component and it is not clear whether they should be classified as clear cell RCC or papillary RCC. In our study we performed an immunohistochemical and genetic analysis of 24 cases of RCC classified as non-classifiable with mixed papillary and clear cell components treated at Clinic of Urology in University Hospital "St. George "-Plovdiv. The mean age of patients was 54.5 years, and gender distribution: 60% male and 40% female. Based on the results of immunohistochemistry and fluorescence in situ hybridization (FISH), patients were stratified in 2 groups. The first group included 16 of the cases where strong immunoreactivity was found for alfa-methyl coenzyme A racemase (AMACR), with cytokeratin 7 (CK7) being present in 15 of these. In all cases in this group, FISH proved trisomy 7 and 17, in 4-9p deletion, and in 2- 3p deletion. The remaining 8 cases were stratified in the second group - all negative for CK7 and only one positive for AMACR. Genetic analysis showed a lack of trisomy 7 and 17 in all cases, as well as a deletion of 3p and 9p in 7 of them. The combination of immunohistochemical and genetic analyzes allows with a high accuracy to differentiate cases of papillary RCC from those with clear cell RCC.


2014 ◽  
Vol 138 (12) ◽  
pp. 1673-1679 ◽  
Author(s):  
Lan L. Gellert ◽  
Rohit Mehra ◽  
Ying-Bei Chen ◽  
Anuradha Gopalan ◽  
Samson W. Fine ◽  
...  

Context While biopsies are now increasingly being performed for the diagnosis of renal cortical neoplasms, the influence of the rendered pathological diagnoses on the clinical management is only rarely documented. Objectives To report our experience with consecutively performed renal biopsies and the potential impact of the diagnosis on subsequent clinical management. Design Material from needle biopsies performed consecutively at our institution between 2006 and 2011 was reviewed. The influence of the reported pathology results on the clinical management was determined from patient follow-up medical record review. Results In total, 218 percutaneous biopsies for renal masses were performed during this period. Among them, 181 (83%) yielded neoplastic tissue, including 81 clear cell renal cell carcinomas, 29 low-grade oncocytic neoplasms, 7 papillary renal cell carcinomas, 5 clear cell papillary renal cell carcinomas, 5 angiomyolipomas, and 14 urothelial carcinomas. Fourteen additional cases (6%) contained lesional material from clinically known nonneoplastic processes, for a total diagnostic yield of 89%. Twenty-three (11%) were nonrepresentative of lesional tissue. In 10 of these, repeat biopsies or resections established the diagnosis of renal tumors. Biopsy diagnosis was confirmed in 29 of 30 cases (97%) on subsequent nephrectomy. Following the biopsy diagnosis, there were significant differences in the clinical management; overall, 79% of clear cell renal cell carcinomas received therapeutic interventions, and 17% were put on active surveillance. In contrast, 77% of the benign or low-grade lesions were put on active surveillance. Conclusions Accurate and specific diagnosis can be rendered on renal core biopsy in most renal tumors, and the biopsy diagnosis can have a definitive role in their clinical management.


2018 ◽  
Vol 60 (3) ◽  
pp. 382-387 ◽  
Author(s):  
Qingqiang Zhu ◽  
Wenrong Zhu ◽  
Jing Ye ◽  
Jingtao Wu ◽  
Wenxin Chen ◽  
...  

Background Few studies have reported on the use of intravoxel incoherent motion (IVIM) for renal tumors. Purpose To investigate the value of IVIM for distinguishing renal tumors. Material and Methods Thirty-one patients with clear cell renal cell carcinomas (CCRCCs), 13 patients with renal angiomyolipomas with minimal fat (RAMFs), eight patients with chromophobe renal cell carcinomas (ChRCCs), and ten patients with papillary renal cell carcinomas (PRCCs) were examined. The tissue diffusivity (D), pseudodiffusivity (D*), and perfusion fraction (f) were calculated. Results The D and f values were highest for CCRCCs, lowest for PRCCs, and intermediate for ChRCCs and RAMFs ( P < 0.05). The D values of CCRCCs differed significantly from those of ChRCCs and PRCCs ( P < 0.05). The D* values were highest for RAMFs, lowest for ChRCCs, and intermediate for CCRCCs and PRCCs ( P < 0.05). Statistically significant differences were observed between the D* values of CCRCCs and RAMFs ( P < 0.05). The D* values of the CCRCCs differed significantly from the D* values of the ChRCCs ( P < 0.05). Using the D and f values of 1.10 and 0.41, respectively, as the threshold values for differentiating CCRCCs from RAMFs, ChRCCs, and PRCCs, the best results had sensitivities of 81.0% and 66.8% and specificities of 85.7% and 81.0%, respectively. Using the D* value of 0.038 as the threshold value for differentiating RAMFs from CCRCCs, ChRCCs, and PRCCs, the best result obtained had a sensitivity of 90.5% and specificity of 76.2%. Conclusion IVIM may provide information for differentiating renal tumor types.


Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 602 ◽  
Author(s):  
Moonsik Kim ◽  
Jin Woo Joo ◽  
Seok Joo Lee ◽  
Yoon Ah Cho ◽  
Cheol Keun Park ◽  
...  

In recent years, renal epithelial tumors have been among the fastest reclassifying tumors, requiring updates to the tumor classification system. Nonetheless, immunohistochemistry (IHC) remains the most widely used tool for renal epithelial tumors. In this proposal, we aimed to create the most efficient IHC panel for categorizing the diverse subtypes of renal tumors, and to find out more specific immunohistochemical results in each subtype or each antibody. A total of 214 renal tumors were analyzed using 10 possible IHC markers to differentiate subtypes, including three major renal cell carcinoma (RCC) subtypes, clear-cell type (50 cases), papillary type (50 cases), and chromophobe type (20 cases), and minor subtypes (MiT RCC, 13 cases; collecting duct carcinoma, 5 cases; and oncocytoma, 10 cases). A triple immunomarker (cytokeratin 7 (CK7)-carbonic anhydrase IX (CAIX)- alpha-methylacyl-CoA racemase (AMACR)) panel is useful in particular high-grade clear-cell tumors. If IHC remains ambiguous, the use of an adjunctive panel can be suggested, including CD10, epithelial membrane antigen, cathepsin K, c-kit, hepatocyte nuclear factor 1-β, and E-cadherin. For an efficient immunohistochemical strategy for subtyping of RCC, we conclude that the CK7-CAIX-AMACR panel is the best primary choice for screening subtyping.


2012 ◽  
Vol 53 (1) ◽  
pp. 112-118 ◽  
Author(s):  
Seung Chai Jung ◽  
Jeong Yeon Cho ◽  
Seung Hyup Kim

Background Subtype differentiation of small renal cell carcinomas (RCCs) can provide more information to surgeons and patients and get more useful information about imaging features of small renal tumors. Purpose To evaluate the usefulness of the measurement of degree and heterogeneity of enhancement in subtype differentiation of small renal cell carcinomas (RCCs) by three-phase multidetector-row CT (MDCT). Material and Methods We reviewed 149 pathologically confirmed small (<4cm) RCCs in 143 patients: 114 (clear cell), 17 (chromophobe), and 18 papillary (8 papillary type 1 and 10 papillary type 2). Scans in pre-contrast, corticomedullary, and nephrographic phases were obtained. We assessed the mean and standard deviation of the Hounsfield units (HU) in a region of interest (ROI) for the degree of enhancement and the heterogeneity of enhancement, respectively. We compared the attenuation values, and the degree and heterogeneity of enhancement among the subtypes. Results The clear cell type showed the highest enhancement and heterogeneity of enhancement followed by chromophobe and papillary types. There was a significant difference in enhancement between the clear cell and papillary types in the corticomedullary phase ( P < 0.01), and between clear and non-clear cell types in the nephrographic phase ( P < 0.05). Heterogeneity of enhancement showed a significant difference between clear cell and non-clear cell types in the corticomedullary phase ( P < 0.05). Conclusion The measurement of degree and heterogeneity of enhancement on contrast-enhanced MDCT may be a simple and useful method to differentiate between the different types of small RCCs.


2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 699-699
Author(s):  
Laurence Albiges ◽  
Damien Pouessel ◽  
Marie Beylot-Barry ◽  
Guido Bens ◽  
Diane Pannier ◽  
...  

699 Background: AcSe Nivolumab (N), is a non-randomised, open-label, multicentric study to investigate the efficacy and safety of nivolumab monotherapy in patients (pts) with specific rare cancers (NCT03012581). We report on the non-clear cell renal cell carcinoma (RCC) cohort. Methods: Primary endpoint was objective response rate (ORR) at 12 weeks according to RECIST1.1. All pts receives N at 240mg IV every 2 weeks. Secondary endpoints included progression free survival (PFS), overall survival (OS), best response, and safety. Results: Between 07/2017 and 02/2019, 50 pts have been enrolled across 13 institutions. Median age was 61.4 years old, 70% were male. ECOG PS was 0, 1, 2, in 29%, 63% and 8% of pts respectively. Histological types were papillary (pRCC) type 2 (41%), chromophobe (18%), pRCC type I (10%), pRCC unclassified (8%), collecting duct carcinoma (CDC) (8%), and others (including predominant sarcomatoid, renal medullary carcinoma, MITF associated RCC, unclassified RCC). N was used in first line in 16%, second line in 54% and third line or beyond in 30%. IMDC risk group was 14%, 70% and 16% for good, intermediate and poor risk respectively. With a median follow up of 10.4 months (mo), 42 pts had discontinued N. The 12 weeks-ORR was 6% (3 PR), with stable disease in 49% and PD in 44% of pts. The best ORR was 10%. Median PFS was 3.9 mo (IC95% [2.9; 8.3]). At time of analysis, 25 pts (50%) had died and 12-months OS rate was 47.7% (IC95% [33.5; 67.8]). Overall, 31 pts (62%) have presented at least one grade ≥ 3 AE. No new safety signal with N was reported. 12 weeks-ORR and best ORR according to distinct histology are presented in table 1. Pts with PR were 1pRCC type 2, 1pRCC type 1, 1 CDC, 1 MITF RCC and 1 unclassified. Conclusions: We report the first prospective study of N single agent in non-clear cell RCC. N demonstrates limited activity in a pretreated and heterogeneous non- clear cell RCC population. Interestingly 1/4 CDC developed PR while no response was noted in chromophobe RCC. Clinical trial information: NCT03012581. [Table: see text]


2020 ◽  
Vol 10 ◽  
Author(s):  
Żaneta Piotrowska ◽  
Michał Niezgoda ◽  
Grzegorz Młynarczyk ◽  
Magdalena Acewicz ◽  
Irena Kasacka

ObjectiveThe Wnt/ß-catenin pathway plays an important role in pathogenesis of variety cancers. Most studies on changes in WNT/β-catenin pathway in renal cell carcinoma (RCC) apply only to clear cell RCC, while there are no comparative assessments of this signaling pathway in various histological types of renal tumors in the available literature. Additionally, considering the close relationship between WNT/β-catenin signaling, CacyBP/SIP and proteasomal activity, it seemed worth comparing WNT/β-catenin pathway, CacyBP/SIP and LMP7 immunoproteasome subunit in human samples of clear cell, papillary, and chromophobe RCC.MethodsTests were performed on sections of three types of kidney tumors together with surrounding unchanged tissue fragments collected from 50 patients. Samples were divided into three groups depending on the histological type of cancer: clear cell, papillary and chromophobe RCC. Immunohistochemistry and PCR methods were used to identify WNT10A, Fzd5, β-catenin, GSK-3ß, CacyBP/SIP, LMP7, and gene expression.ResultsImmunoreactivity and expression of WNT10A, Fzd5, β-catenin, GSK-3ß, CacyBP/SIP, LMP7 in clear cell RCC was markedly increased compared to non-cancerous kidney tissue. In papillary RCC, immunoreactivity and expression of WNT/β-catenin pathway, CacyBP/SIP, LMP7 was also increased compared to non-malignant kidneys, but it was less pronounced than in clear cell RCC. The least substantial increase in immunoreactivity and expression of WNT/β-catenin pathway, CacyBP/SIP, LMP7 was found in chromophobe RCC, compared to other RCC histological subtypes studied.ConclusionsStudy results suggest an important role of WNT/β-catenin pathway, CacyBP/SIP and LMP7 in RCC carcinogenesis, and may indicate new aspects of pathomechanisms leading to differences in the biology of clear cell, papillary and chromophobe RCC.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15077-e15077
Author(s):  
Urbano Anido ◽  
Vanessa Medina Villaamil ◽  
Guadalupe Aparicio Gallego ◽  
Maria Quindós Varela ◽  
Sergio Vazquez-Estevez ◽  
...  

e15077 Background: Renal cell carcinomas (RCC) constitute a morphologically and genetically heterogeneous tumor.Wnt proteins are a large family of secreted glycoproteins that activate intracellular signal transduction pathways to control a wide variety of cellular processes such as determination of cell fate, proliferation, migration, and polarity.Wnt signalling may be playing a central role during RCC development. Methods: To characterize Wnt signalling activity in RCC, we gathered 48 tumor samples from patients diagnosed with metastatic RCC between years 2006 and 2011. Expression levels of Wnt family members (Wnt1, Wnt2, Wnt3a, Wnt4, Wnt5a, Wnt7a, and Wnt9a) were examined by real-time PCR and immunohistochemistry in tumor and normal tissue from removed kidneys. Results: Wnt1 and Wnt5a were up-regulated in clear cell RCC being their relative expression 2.4.103 (Wnt1) and 4.102 (Wnt5a) times higher in renal tumor tissue than in normal tissue. One-way ANOVA test showed Wnt3a and Wnt4 as the best protein markers to distinguish clear cell RCC (F=3.95, p=0.010 and F=3.05, p=0.029, respectively). Wnt1 and Wnt7a were over-expressed in those cases which had undergone nefrectomy (Mann-Whitney U test p=0.065 and p=0.056 respectively). Finally, Wnt2 protein level was associated with those patients with high risk prognosis (Kruskal-Wallis test p=0.001). Conclusions: Our results indicate that Wnt3a and Wnt4 are potentially useful immunohistochemical markers for the differential diagnosis between clear cell RCC and other subtypes of RCC and also suggest a role for Wnt2 as a high risk prognosis marker.


2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
Antonios Katsimantas ◽  
Spyridon Paparidis ◽  
Konstantinos Bouropoulos ◽  
Nikolaos Ferakis

Sporadic, synchronous, bilateral, or unilateral Renal Cell Carcinomas constitute a rare clinical entity. We report the case of a 68-year-old male patient who presented in our department due to incidentally discovered multiple, bilateral renal tumors. Magnetic Resonance Imaging demonstrated cT1b renal tumors at the lower pole of each kidney and a cT1a renal tumor at the upper pole of the right kidney. The patient underwent transperitoneal, laparoscopic left partial nephrectomy with renal artery occlusion, histology revealed high-grade, pT1b, clear-cell renal cell carcinoma; however we observed decline of patient’s estimated glomerular filtration rate postoperatively. Forty days postoperatively, he underwent open partial nephrectomy for the right sided tumors with manual compression of the renal parenchyma and no use of ischemia. Histology revealed high-grade, pT1a, clear-cell renal cell carcinoma at the upper pole of the right kidney and low-grade, pT1b, clear-cell renal cell carcinoma at the lower pole of the right kidney. There was no additional decline in the serum creatinine value postoperatively. The patient avoided permanent or temporary dialysis and 6 months postoperatively he demonstrated no recurrence on imaging and his renal function remained stable.


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