= Discovery stage.
= Translation stage.
= Clinically available.
MSACL 2019 EU : Do

MSACL 2019 EU Abstract

Self-Classified Topic Area(s): Tissue Imaging

Mass Spectrometric Imaging of Cysteine Rich Proteins in Human Skin

Tomas Do (1), Lucie Vanickova (1,2), Roman Guran (1,2), Sandor Kollar (3), Gabriella Emri (4), Sona Krizkova (1,2), Zbynek Heger (1,2), Ondrej Zitka (1,2), Vojtech Adam (1,2)
(1) Mendel University, Brno, Czech Republic (2) Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic (3) Kenezy Gyula County Hospital, Debrecen, Hungary (4) University of Debrecen, Debrecen, Hungary


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 Tomas Do (Presenter)
Mendel University

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Relevant Financial Disclosures (within past 24 months)
No relevant financial relationship(s) to disclose.

Abstract

Introduction: Looking insight pathological processes, metallothioneins (MTs) are considered to be potential biomarkers for monitoring of a development of various types of diseases, such as cancer. The early identification of the MTs in biological tissues could be important tool for the estimation of appropriate clinical therapy.

Objectives: The aim of this study was to investigate the application of matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) together with immunohistochemical analyses (IHC) using MT-1/2 antibody for MT detection in biopsy specimens of human skin.

Methods: Formalin-fixed paraffin-embedded (FFPE) tissue blocks of various types of skin cancers were selected for analysis. Normal skin was derived from an 83-year-old female patient, who had a keratoacanthoma on her forearm. The resection margin free of any tumour cells was used for the study. Basal cell cancer (basalioma solidum et cysticum) was localized on the shoulder of a 61-year-old male patient. Superficially spreading malignant melanoma with Breslow tumour thickness 2.76 mm, Clark level III, 0–2/hpf mitotic activity (pT3a) was removed from the thigh of a 47-year-old male patient. Grade 2 cutaneous squamous cell cancer of an 86-year-old female patient was localized on her nose. Melanocytic nevus was removed from the chest of a 45-year-old female patient. FFPE tissues were histologically characterized, analyzed by MALDI MSI, and immunohistologically stained.

Results: Principal component analyses of MSI data revealed differences in the peptide/protein profiles separating healthy skin from the carcinoma specimens. Statistically significant ion peaks at m/z 6038, 6300, 6676, and 7026 were more frequently detected in squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and melanoma. Using IHC, we found that MT-1/2 was significantly higher in SCC and melanoma compared to healthy skin. Surprisingly, significantly low levels of MT-1/2 were found in BCC.

Conclusion: The results indicate important role of MTs in melanoma occurrence and progression. There are hidden processes associated with MTs based on differences of the occurrence of the MS peaks, which could be associated with cycling of MTs isoforms. In conclusion, our results contributed to the basic knowledge on protein distribution in histologically specified regions in skin cancer tissues.