Papathomas, T.* ; Tzortzakakis, A.* ; Sun, N. ; Erlmeier, F.* ; Feuchtinger, A. ; Trpkov, K.* ; Bazarova, A.* ; Arvanitis, A.* ; Wang, W.* ; Bozoky, B.* ; Kokaraki, G.* ; Axelsson, R.* ; Walch, A.K.
     
 
    
        
In situ metabolomics expands the spectrum of renal tumours positive on 99mTc-sestamibi single photon emission computed tomography/computed tomography examination.
    
    
        
    
    
        
        Eu. Urol. Open Sci. 22, 88-96 (2020)
    
    
    
		
		
			
				Background: Definite noninvasive characterisation of renal tumours positive on 99mTc-sestamibi single photon emission computed tomography/computed tomography (SPECT/CT) examination including renal oncocytomas (ROs), hybrid oncocytic chromophobe tumours (HOCTs), and chromophobe renal cell carcinoma (chRCC) is currently not feasible. Objective: To investigate whether combined 99mTc-sestamibi SPECT/CT and in situ metabolomic profiling can accurately characterise renal tumours exhibiting 99mTc-sestamibi uptake. Design, setting, and participants: A tissue microarray analysis of 33 tumour samples from 28 patients was used to investigate whether their in situ metabolomic status correlates with their features on 99mTc-sestamibi SPECT/CT examination. In order to validate emerging data, an independent cohort comprising 117 tumours was subjected to matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI MSI). Outcome measurements and statistical analysis: MALDI MSI data analysis and image generation were facilitated by FlexImaging v. 4.2, while k-means analysis by SCiLS Lab software followed by R-package CARRoT analysis was used for assessing the highest predictive power in the differential of RO versus chRCC. Heatmap-based clustering, sparse partial least-squares discriminant analysis, and volcano plots were created with MetaboAnalyst 3.0. Results and limitations: We identified a discriminatory metabolomic signature for 99mTc-sestamibi SPECT/CT–positive Birt-Hogg-Dubè–associated HOCTs versus other renal oncocytic tumours. Metabolomic differences were also evident between 99mTc-sestamibi–positive and 99mTc-sestamibi–negative chRCCs, prompting additional expert review; two of three 99mTc-sestamibi–positive chRCCs were reclassified as low-grade oncocytic tumours (LOTs). Differences were identified between distal-derived tumours from those of proximal tubule origin, including differences between ROs and chRCCs. Conclusions: The current study expands the spectrum of 99mTc-sestamibi SPECT/CT–positive renal tumours, encompassing ROs, HOCTs, LOTs, and chRCCs, and supports the feasibility of in situ metabolomic profiling in the diagnostics and classification of renal tumours. Patient summary: For preoperative evaluation of solid renal tumours, 99mTc-sestamibi single photon emission computed tomography/computed tomography (SPECT/CT) is a novel examination method. To increase diagnostic accuracy, we propose that 99mTc-sestamibi–positive renal tumours should be biopsied and followed by a combined histometabolomic analysis.
			
			
				
			
		 
		
			
				
					
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        Publikationstyp
        Artikel: Journalartikel
    
 
    
        Dokumenttyp
        Wissenschaftlicher Artikel
    
 
    
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        Herausgeber
        
    
    
        Schlagwörter
        99mtc-sestamibi Spect/ct ; Renal Tumour/in Situ Metabolomics; Molecular Characterization; Intratumor Heterogeneity; Cell; Metabolites; Oncocytoma; Carcinoma
    
 
    
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        Sprache
        englisch
    
 
    
        Veröffentlichungsjahr
        2020
    
 
    
        Prepublished im Jahr 
        
    
 
    
        HGF-Berichtsjahr
        2020
    
 
    
    
        ISSN (print) / ISBN
        2666-1691
    
 
    
        e-ISSN
        2666-1683
    
 
    
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	    Band: 22,  
	    Heft: ,  
	    Seiten: 88-96 
	    Artikelnummer: ,  
	    Supplement: ,  
	
    
 
  
        
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            Verlag
            Elsevier
        
 
        
            Verlagsort
            Radarweg 29, 1043 Nx Amsterdam, Netherlands
        
 
	
        
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        Begutachtungsstatus
        Peer reviewed
    
 
     
    
        POF Topic(s)
        30205 - Bioengineering and Digital Health
30505 - New Technologies for Biomedical Discoveries
    
 
    
        Forschungsfeld(er)
        Enabling and Novel Technologies
    
 
    
        PSP-Element(e)
        G-500390-001
A-630600-001
    
 
    
        Förderungen
        VINNOVA
    
 
    
        Copyright
        
    
 	
    
    
    
    
    
        Erfassungsdatum
        2020-12-20