Microproteomic Profiling of High‐Grade Squamous Intraepithelial Lesion of the Cervix: Insight into Biological Mechanisms of Dysplasia and New Potential Diagnostic Markers

Pottier, Charles; Kriegsmann, Mark; Alberts, Deborah; Smargiasso, Nicolas; Baiwir, Dominique; Mazzucchelli, Gabriel; Herfs, Michaël; Fresnais, Margaux; Casadonte, Rita; Delvenne, Philippe; Pauw, Edwin De; Longuespée, Rémi

doi:10.1002/prca.201800052

Cited by 15 publications

(26 citation statements)

References 64 publications

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“…Regardless of the study design, there is consensus concerning the significantly higher specificity and positive predictive value of p16/Ki‐67 immunocytochemistry in tissue specimen compared to cytology or human papilloma virus DNA test results . In the present preliminary investigation, we detected areas of intraepithelial neoplasia by MALDI imaging which may be a starting point for the mass spectrometric diagnosis of cervical intraepithelial neoplasia in squamous and glandular epithelium …”

Section: Discussionmentioning

confidence: 77%

MALDI Imaging for Proteomic Painting of Heterogeneous Tissue Structures

Kriegsmann¹,

Kriegsmann

Kriegsmann³

et al. 2018

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Purpose To present matrix‐assisted laser desorption/ionization (MALDI) imaging as a powerful method to highlight various tissue compartments. Experimental design Formalin‐fixed paraffin‐embedded (FFPE) tissue of a uterine cervix, a pancreas, a duodenum, a teratoma, and a breast cancer tissue microarray (TMA) are analyzed by MALDI imaging and by immunohistochemistry (IHC). Peptide images are visualized and analyzed using FlexImaging and SCiLS Lab software. Different histological compartments are compared by hierarchical cluster analysis. Results MALDI imaging highlights tissue compartments comparable to IHC. In cervical tissue, normal epithelium can be discerned from intraepithelial neoplasia. In pancreatic and duodenal tissues, m/z signals from lymph follicles, vessels, duodenal mucosa, normal pancreas, and smooth muscle structures can be visualized. In teratoma, specific m/z signals to discriminate squamous epithelium, sebaceous glands, and soft tissue are detected. Additionally, tumor tissue can be discerned from the surrounding stroma in small tissue cores of TMAs. Proteomic data acquisition of complex tissue compartments in FFPE tissue requires less than 1 h with recent mass spectrometers. Conclusion and clinical relevance The simultaneous characterization of morphological and proteomic features in the same tissue section adds proteomic information for histopathological diagnostics, which relies at present on conventional hematoxylin and eosin staining, histochemical, IHC and molecular methods.

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Section: Discussionmentioning

confidence: 77%

MALDI Imaging for Proteomic Painting of Heterogeneous Tissue Structures

Kriegsmann¹,

Kriegsmann

Kriegsmann³

et al. 2018

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“…In a recent investigation, cervical normal squamous (ectocervix), columnar (endocervix) epithelium, and cervical high‐grade squamous intraepithelial lesion (HSIL) were compared by LC‐MS/MS. HSIL are precancerous lesions leading to squamous cell carcinoma (SqCC) of the uterine cervix . Without treatment, it has been estimated that 30–50% of HSIL evolve to SqCC of the cervix .…”

Section: Correlation Of M/z Values Found By Maldi Imaging With Massesmentioning

confidence: 99%

Identification of MALDI Imaging Proteolytic Peptides Using LC‐MS/MS‐Based Biomarker Discovery Data: A Proof of Concept

Longuespée

Casadonte³

et al. 2018

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Purpose Identification of proteolytic peptides from matrix‐assisted laser desorption/ionization (MALDI) imaging remains a challenge. The low fragmentation yields obtained using in situ post source decay impairs identification. Liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) is an alternative to in situ MS/MS, but leads to multiple identification candidates for a given mass. The authors propose to use LC‐MS/MS‐based biomarker discovery results to reliably identify proteolytic peptides from MALDI imaging. Experimental design The authors defined m/z values of interest for high grade squamous intraepithelial lesion (HSIL) by MALDI imaging. In parallel the authors used data from a biomarker discovery study to correlate m/z from MALDI imaging with masses of peptides identified by LC‐MS/MS in HSIL. The authors neglected candidates that were not significantly more abundant in HSIL according to the biomarker discovery investigation. Results The authors assigned identifications to three m/z of interest. The number of possible identifiers for MALDI imaging m/z peaks using LC‐MS/MS‐based biomarker discovery studies was reduced by about tenfold compared using a single LC‐MS/MS experiment. One peptide identification candidate was validated by immunohistochemistry. Conclusion and clinical relevance This concept combines LC‐MS/MS‐based quantitative proteomics with MALDI imaging and allows reliable peptide identification. Public datasets from LC‐MS/MS biomarker discovery experiments will be useful to identify MALDI imaging m/z peaks.

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“…LC‐MS/MS‐based shotgun proteomics of tissue can now be performed at a very small scale. Microproteomics allowed us to depict the landscape of proteins associated with high‐grade squamous intraepithelial lesions (HSIL) of the uterine cervix . Such protein maps improve our understanding of the biological background of cervical dysplasia and may contribute to finding new diagnostic or therapeutic targets.…”

mentioning

confidence: 99%

“…In this specific study, we found a nuclear marker—the histone chaperone ASF1B—allowing for the distinction between normal ectocervical epithelium and low‐ and high‐grade dysplastic lesions of the ectocervix. This distinction is highly relevant in pathological diagnostics, since low‐ and high‐grade lesions have different prognosis and lead to different patient monitoring …”

mentioning

confidence: 99%

“…Hoffmann et al performed LC‐MS/MS analyses of proteins from tissues analyzed by MALDI imaging in order to assign identification of m / z peaks in head and neck cancer . Using the dataset for microproteomic profiling of cervical dysplasia, we correlated the mass of proteolytic peptides from HSIL biomarker proteins with m / z values found in higher intensity in HSIL by MALDI imaging. We demonstrated that LC‐MS/MS‐based biomarker discovery data allowed for a more reliable identification of signature m / z values from MALDI imaging …”

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confidence: 99%

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