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Huber, K. ; Kunzke, T. ; Buck, A. ; Langer, R.* ; Luber, B.* ; Feuchtinger, A. ; Walch, A.K.

Multimodal analysis of formalin-fixed and paraffin-embedded tissue by MALDI imaging and fluorescence in situ hybridization for combined genetic and metabolic analysis.

Lab. Invest. 99, 1535-1546 (2019)
Verlagsversion Preprint Forschungsdaten DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Multimodal tissue analyses that combine two or more detection technologies provide synergistic value compared to single methods and are employed increasingly in the field of tissue-based diagnostics and research. Here, we report a technical pipeline that describes a combined approach of HER2/CEP17 fluorescence in situ hybridization (FISH) analysis with MALDI imaging on the very same section of formalin-fixed and paraffin-embedded (FFPE) tissue. FFPE biopsies and a tissue microarray of human gastroesophageal adenocarcinoma were analyzed by MALDI imaging. Subsequently, the very same section was hybridized by HER2/CEP17 FISH. We found that tissue morphology of both, the biopsies and the tissue microarray, was unaffected by MALDI imaging and the HER2 and CEP17 FISH signals were analyzable. In comparison with FISH analysis of samples without MALDI imaging, we observed no difference in terms of fluorescence signal intensity and gene copy number. Our combined approach revealed adenosine monophosphate, measured by MALDI imaging, as a prognostic marker. HER2 amplification, which was detected by FISH, is a stratifier between good and poor patient prognosis. By integrating both stratification parameters on the basis of our combined approach, we were able to strikingly improve the prognostic effect. Combining molecules detected by MALDI imaging with the gene copy number detected by HER2/CEP17 FISH, we found a synergistic effect, which enhances patient prognosis. This study shows that our combined approach allows the detection of genetic and metabolic properties from one very same FFPE tissue section, which are specific for HER2 and hence suitable for prognosis. Furthermore, this synergism might be useful for response prediction in tumors.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Mass-spectrometry; Clinical Pathology; Prostate-cancer; Breast-cancer; Her2; Trastuzumab; Growth
ISSN (print) / ISBN 0023-6837
e-ISSN 1530-0307
Zeitschrift Laboratory Investigation
Quellenangaben Band: 99, Heft: 10, Seiten: 1535-1546 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort 75 Varick St, 9th Flr, New York, Ny 10013-1917 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Analytical Pathology (AAP)