Abstract
PurposeMedulloblastoma, the most common primary pediatric malignant brain tumor, originates in the posterior fossa of the brain. Pineoblastoma, which originates within the pineal gland, is a rarer malignancy that also presents in the pediatric population. Medulloblastoma and pineoblastoma exhibit overlapping clinical features and have similar histopathological characteristics. Histopathological similarities confound rapid diagnoses of these two tumor types. We have conducted a pilot feasibility study analyzing the molecular profile of archived frozen human tumor specimens using mass spectrometry imaging (MSI) to identify potential biomarkers capable of classifying and distinguishing between medulloblastoma and pineoblastoma.MethodsWe performed matrix-assisted laser desorption ionization Fourier transform ion cyclotron resonance mass spectrometry imaging on eight medulloblastoma biopsy specimens and three pineoblastoma biopsy specimens. Multivariate statistical analyses were performed on the MSI dataset to generate classifiers that distinguish the two tumor types. Lastly, the molecules that were discriminative of tumor type were queried against the Lipid Maps database and identified.ResultsIn this pilot study we show that medulloblastoma and pineoblastoma can be discriminated using molecular profiles determined by MSI. The highest-ranking discriminating classifiers of medulloblastoma and pineoblastoma were glycerophosphoglycerols and sphingolipids, respectively.ConclusionWe demonstrate proof-of-concept that medulloblastoma and pineoblastoma can be rapidly distinguished by using MSI lipid profiles. We identified biomarker candidates capable of distinguishing these two histopathologically similar tumor types. This work expands the current molecular knowledge of medulloblastoma and pineoblastoma by characterizing their lipidomic profiles, which may be useful for developing novel diagnostic, prognostic and therapeutic strategies.
Highlights
Medulloblastoma (MB) is the most common primary pediatric malignant brain tumor, originates in the posterior fossa, and has high-grade embryonal features [1, 2]
We performed matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) on MB and PB tissue sections to determine if the spectral profiles of the two tumor types differed
Following pathology review of post-analysis hematoxylin and eosin (H&E) stained sections, we focused the MALDI MSI data analyses on areas of dense tumor so as to identify molecules that were preferentially detected in tumor tissue
Summary
Medulloblastoma (MB) is the most common primary pediatric malignant brain tumor, originates in the posterior fossa, and has high-grade embryonal features [1, 2]. Extended author information available on the last page of the article on DNA aberrations and molecular profiling, MB tumors are subgrouped as either: Wnt-signaling pathway (WNT)activated; Shh-signaling pathway (SHH)-activated, further subdivided into wild-type or mutant TP53; group 3; group 4 [3, 4]. There have been occasional reports whereby MB tumors may be misclassified as pineoblastoma (PB) when diagnosed based on histopathology without molecular or radiological information [5]. Like MB, these tumors tend to occur in pediatric patients and display high-grade embryonal morphology [6]. PB has a propensity to spread through the cerebrospinal fluid and is associated with a poor prognosis [6]
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