In Situ Metabolomics Expands the Spectrum of Renal Tumours Positive on Tc-sestamibi Single Photon Emission Computed Tomography/Computed Tomography Examination.

BACKGROUND

Definite noninvasive characterisation of renal tumours positive on Tc-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 Tc-sestamibi SPECT/CT and in situ metabolomic profiling can accurately characterise renal tumours exhibiting Tc-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 Tc-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 Tc-sestamibi SPECT/CT-positive Birt-Hogg-Dubè-associated HOCTs versus other renal oncocytic tumours. Metabolomic differences were also evident between Tc-sestamibi-positive and Tc-sestamibi-negative chRCCs, prompting additional expert review; two of three Tc-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 Tc-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, Tc-sestamibi single photon emission computed tomography/computed tomography (SPECT/CT) is a novel examination method. To increase diagnostic accuracy, we propose that Tc-sestamibi-positive renal tumours should be biopsied and followed by a combined histometabolomic analysis.