Molecular signatures of medullary thyroid carcinoma by matrix-assisted laser desorption/ionisation mass spectrometry imaging

Smith, Andrew; Galli, Manuel; Piga, Isabella; Denti, Vanna; Stella, Martina; Chinello, Clizia; Fusco, Nicola; Leni, Davide; Manzoni, Marco; Roversi, Gaia; Garancini, Mattia; Pincelli, Angela Ida; Cimino, Vincenzo; Capitoli, Giulia; Magni, Fulvio; Pagni, Fabio

doi:10.1016/j.jprot.2018.03.021

Cited by 37 publications

(31 citation statements)

References 33 publications

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“…In recent years, MALDI-MSI of tryptic peptides generated from FFPE sections has been increasingly used for tumor classification and the discovery of putative disease biomarkers (22–25). The use of FFPE sections rather than fresh-frozen tissues extends the technique to a vast store of archival pathology specimens.…”

Section: Discussionmentioning

confidence: 99%

Novel Prognostic Markers in Triple-Negative Breast Cancer Discovered by MALDI-Mass Spectrometry Imaging

2019

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There are no widely-accepted prognostic markers currently available to predict outcomes in patients with triple-negative breast cancer (TNBC), and no targeted therapies with confirmed benefit. We have used MALDI mass spectrometry imaging (MSI) of tryptic peptides to compare regions of cancer and benign tissue in 10 formalin-fixed, paraffin-embedded sections of TNBC tumors. Proteins were identified by reference to a peptide library constructed by LC-MALDI-MS/MS analyses of the same tissues. The prognostic significance of proteins that distinguished between cancer and benign regions was estimated by Kaplan-Meier analysis of their gene expression from public databases. Among peptides that distinguished between cancer and benign tissue in at least 3 tissues with a ROC area under the curve >0.7, 14 represented proteins identified from the reference library, including proteins not previously associated with breast cancer. Initial network analysis using the STRING database showed no obvious functional relationships except among collagen subunits COL1A1, COL1A2, and COL63A, but manual curation, including the addition of EGFR to the analysis, revealed a unique network connecting 10 of the 14 proteins. Kaplan-Meier survival analysis to examine the relationship between tumor expression of genes encoding the 14 proteins, and recurrence-free survival (RFS) in patients with basal-like TNBC showed that, compared to low expression, high expression of nine of the genes was associated with significantly worse RFS, most with hazard ratios >2. In contrast, in estrogen receptor-positive tumors, high expression of these genes showed only low, or no, association with worse RFS. These proteins are proposed as putative markers of RFS in TNBC, and some may also be considered as possible targets for future therapies.

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Section: Discussionmentioning

confidence: 99%

Novel Prognostic Markers in Triple-Negative Breast Cancer Discovered by MALDI-Mass Spectrometry Imaging

2019

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“…To maximize the homogeneity in preanalytical variables, cases were selected from a unique institution with available trackable processing phases. For this study, fixation time was set at 24 hours following the surgical procedure, as previously described [6]. Tissues subsequently were grossed and processed as routine cases; a representative histological hematoxylin and eosin (H&E) stained section of the original nodules was evaluated by two lung-committed pathologists (FB, FP) avoiding little fixed areas of necrosis and fibrosis and the corresponding paraffin block was chosen for the study.…”

Section: Methodsmentioning

confidence: 99%

The Reproducibility of the Immunohistochemical PD-L1 Testing in Non-Small-Cell Lung Cancer: A Multicentric Italian Experience

Vigliar¹,

Malapelle²,

Bono

et al. 2019

BioMed Research International

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An important harmonization effort was produced by the scientific community to standardize both the preanalytical and interpretative phases of programmed death-ligand 1 (PD-L1) immunohistochemical (IHC) testing in non-small-cell lung cancer (NSCLC). This analysis is crucial for the selection of patients with advanced-stage tumors eligible for treatment with pembrolizumab and potentially with other anti-PD-1/PD-L1 checkpoint inhibitors. This multicentric retrospective study evaluated the reproducibility of PD-L1 testing in the Italian scenario both for closed and open platforms. In the evaluation of the well-known gold-standard combinations (Agilent 22C3 PharmDx on Dako Autostainer versus Roche’s Ventana SP263 on BenchMark), the results confirmed the literature data and showed complete overlapping between the two methods. With regard to the performances by using open platforms, the combination of 22C3 with Dako Omnis or Benchmark obtained good results basically, while the 28,8 clone seemed to be associated with worse scores.

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“…As intact proteins are not accessible for direct MALDI–MSI, tryptic peptides form the bulk of MALDI–MSI studies using FFPE samples. This has been particularly useful for investigating clinically relevant questions where typical histomorphological analysis may be ambiguous, e.g., classifying thyroid cancers, identifying metastasis origin, and discriminating between benign and malignant skin lesions . MALDI–MSI has been used for retrospective studies, such as identifying proteins associated with lymph node metastases from primary endometrial cancer .…”

Section: Introductionmentioning

confidence: 99%

Site‐to‐Site Reproducibility and Spatial Resolution in MALDI–MSI of Peptides from Formalin‐Fixed Paraffin‐Embedded Samples

Longuespée

Casadonte³

et al. 2019

Proteomics Clinical Apps

100

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Purpose To facilitate the transition of MALDI–MS Imaging (MALDI–MSI) from basic science to clinical application, it is necessary to analyze formalin‐fixed paraffin‐embedded (FFPE) tissues. The aim is to improve in situ tryptic digestion for MALDI–MSI of FFPE samples and determine if similar results would be reproducible if obtained from different sites. Experimental Design FFPE tissues (mouse intestine, human ovarian teratoma, tissue microarray of tumor entities sampled from three different sites) are prepared for MALDI–MSI. Samples are coated with trypsin using an automated sprayer then incubated using deliquescence to maintain a stable humid environment. After digestion, samples are sprayed with CHCA using the same spraying device and analyzed with a rapifleX MALDI Tissuetyper at 50 µm spatial resolution. Data are analyzed using flexImaging, SCiLS, and R. Results Trypsin application and digestion are identified as sources of variation and loss of spatial resolution in the MALDI–MSI of FFPE samples. Using the described workflow, it is possible to discriminate discrete histological features in different tissues and enabled different sites to generate images of similar quality when assessed by spatial segmentation and PCA. Conclusions and Clinical Relevance Spatial resolution and site‐to‐site reproducibility can be maintained by adhering to a standardized MALDI–MSI workflow.

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Molecular signatures of medullary thyroid carcinoma by matrix-assisted laser desorption/ionisation mass spectrometry imaging

Cited by 37 publications

References 33 publications

Novel Prognostic Markers in Triple-Negative Breast Cancer Discovered by MALDI-Mass Spectrometry Imaging

Novel Prognostic Markers in Triple-Negative Breast Cancer Discovered by MALDI-Mass Spectrometry Imaging

The Reproducibility of the Immunohistochemical PD-L1 Testing in Non-Small-Cell Lung Cancer: A Multicentric Italian Experience

Site‐to‐Site Reproducibility and Spatial Resolution in MALDI–MSI of Peptides from Formalin‐Fixed Paraffin‐Embedded Samples

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