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Cell differentiation in cardiac myxomas: confocal microscopy and gene expression analysis after laser capture microdissection

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Abstract

Cardiac myxomas are rare tumors with a heterogeneous cell population including properly neoplastic (lepidic), endothelial and smooth muscle cells. The assessment of neoplastic (lepidic) cell differentiation pattern is rather difficult using conventional light microscopy immunohistochemistry and/or whole tissue extracts for mRNA analyses. In a preliminary study, we investigated 20 formalin-fixed and paraffin-embedded cardiac myxomas by means of conventional immunohistochemistry; in 10/20 cases, cell differentiation was also analyzed by real-time RT-PCR after laser capture microdissection of the neoplastic cells, whereas calretinin and endothelial antigen CD31 immunoreactivity was localized in 4/10 cases by double immunofluorescence confocal microscopy. Gene expression analyses of α-smooth muscle actin, endothelial CD31 antigen, alpha-cardiac actin, matrix metalloprotease-2 (MMP2) and tissue inhibitor of matrix metalloprotease-1 (TIMP1) was performed on cDNA obtained from either microdissected neoplastic cells or whole tumor sections. We found very little or absent CD31 and α-Smooth Muscle Actin expression in the microdissected cells as compared to the whole tumors, whereas TIMP1 and MMP2 genes were highly expressed in both ones, greater levels being found in patients with embolic phenomena. α-Cardiac Actin was not detected. Confocal microscopy disclosed two different signals corresponding to calretinin-positive myxoma cells and to endothelial CD31-positive cells, respectively. In conclusion, the neoplastic (lepidic) cells showed a distinct gene expression pattern and no consistent overlapping with endothelial and smooth muscle cells or cardiac myocytes; the expression of TIMP1 and MMP2 might be related to clinical presentation; larger series studies using also systematic transcriptome analysis might be useful to confirm the present results.

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Histopathology Department, Pisa University Hospital, Pisa, Italy

    Angela Pucci, Claudia Mattioli, Daniele Lorenzini & Beatrice Belgio

  2. Institute of Life Sciences, Scuola Superiore “Sant’Anna”, Pisa, Italy

    Claudia Mattioli & Marco Matteucci

  3. Hematology Department, Pisa University, Pisa, Italy

    Francesca Panvini & Simone Pacini

  4. Unit of Medical Histology and Embryology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

    Chiara Ippolito & Amelio Dolfi

  5. Cardiac Surgery Department, Pisa University, Pisa, Italy

    Michele Celiento, Andrea De Martino & Uberto Bortolotti

  6. Pathology Department, University of Catania, Catania, Italy

    Giovanni Bartoloni

  7. Pisa University, Pisa, Italy

    Angela Pucci & Fulvio Basolo

Authors
  1. Angela Pucci
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  2. Claudia Mattioli
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  3. Marco Matteucci
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  4. Daniele Lorenzini
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  5. Francesca Panvini
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  6. Simone Pacini
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  7. Chiara Ippolito
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  8. Michele Celiento
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  9. Andrea De Martino
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  10. Amelio Dolfi
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  11. Beatrice Belgio
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  12. Uberto Bortolotti
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  13. Fulvio Basolo
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  14. Giovanni Bartoloni
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Corresponding author

Correspondence to Angela Pucci.

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Pucci, A., Mattioli, C., Matteucci, M. et al. Cell differentiation in cardiac myxomas: confocal microscopy and gene expression analysis after laser capture microdissection. Heart Vessels 33, 1403–1410 (2018). https://doi.org/10.1007/s00380-018-1189-2

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  • DOI: https://doi.org/10.1007/s00380-018-1189-2

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