Metabolite profiling in retinoblastoma identifies novel clinicopathological subgroups.
BACKGROUND
Tumour classification, based on histopathology or molecular pathology, is of value to predict tumour behaviour and to select appropriate treatment. In retinoblastoma, pathology information is not available at diagnosis and only exists for enucleated tumours. Alternative methods of tumour classification, using noninvasive techniques such as magnetic resonance spectroscopy, are urgently required to guide treatment decisions at the time of diagnosis.


METHODS
High-resolution magic-angle spinning magnetic resonance spectroscopy (HR-MAS MRS) was undertaken on enucleated retinoblastomas. Principal component analysis and cluster analysis of the HR-MAS MRS data was used to identify tumour subgroups. Individual metabolite concentrations were determined and were correlated with histopathological risk factors for each group.


RESULTS
Multivariate analysis identified three metabolic subgroups of retinoblastoma, with the most discriminatory metabolites being taurine, hypotaurine, total-choline and creatine. Metabolite concentrations correlated with specific histopathological features: taurine was correlated with differentiation, total-choline and phosphocholine with retrolaminar optic nerve invasion, and total lipids with necrosis.


CONCLUSIONS
We have demonstrated that a metabolite-based classification of retinoblastoma can be obtained using ex vivo magnetic resonance spectroscopy, and that the subgroups identified correlate with histopathological features. This result justifies future studies to validate the clinical relevance of these subgroups and highlights the potential of in vivo MRS as a noninvasive diagnostic tool for retinoblastoma patient stratification.
School of Cancer Sciences, University of Birmingham, Vincent Drive, Birmingham B15 2TT, UK.
Sarah
S
Kohe
Department of Histopathology, Birmingham Children's Hospital, Steelhouse Lane, Birmingham, B4 6NH, UK.
Marie-Anne
MA
Brundler
Department of Oncology, Birmingham Children's Hospital, Steelhouse Lane, Birmingham B4 6NH, UK.
Helen
H
Jenkinson
Department of Ophthalmology, Birmingham Children's Hospital, Steelhouse Lane, Birmingham B4 6NH, UK.
Manoj
M
Parulekar
School of Cancer Sciences, University of Birmingham, Vincent Drive, Birmingham B15 2TT, UK.
Martin
M
Wilson
School of Cancer Sciences, University of Birmingham, Vincent Drive, Birmingham B15 2TT, UK.|Department of Oncology, Birmingham Children's Hospital, Steelhouse Lane, Birmingham B4 6NH, UK.
Andrew C
AC
Peet
School of Cancer Sciences, University of Birmingham, Vincent Drive, Birmingham B15 2TT, UK.
Carmel M
CM
McConville
D000293:Adolescent; D000328:Adult; D000369:Aged, 80 and over; D002454:Cell Differentiation / Q000502:physiology; D002648:Child; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D055442:Metabolome / Q000502:physiology*; D008875:Middle Aged; D010767:Phosphorylcholine / Q000378:metabolism; D025341:Principal Component Analysis / Q000379:methods; D012175:Retinoblastoma / Q000378:metabolism* / Q000473:pathology*; D013654:Taurine / Q000031:analogs & derivatives / Q000378:metabolism; D055815:Young Adult
D010767:Phosphorylcholine; D013654:Taurine; C003949:hypotaurine; D003401:Creatine; D002794:Choline