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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)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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
Korrespondenzautor
Schlagwörter 99mtc-sestamibi Spect/ct ; Renal Tumour/in Situ Metabolomics; Molecular Characterization; Intratumor Heterogeneity; Cell; Metabolites; Oncocytoma; Carcinoma
ISSN (print) / ISBN 2666-1691
e-ISSN 2666-1683
Zeitschrift European Urology Open Science
Quellenangaben Band: 22, Heft: , Seiten: 88-96 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort Radarweg 29, 1043 Nx Amsterdam, Netherlands
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Analytical Pathology (AAP)
Förderungen VINNOVA