Cardiac myxoma cells exhibit embryonic endocardial stem cell features

The origin of myxoma, the most frequent tumour of the heart, remains uncertain. Previous phenotypic characterizations have shown heterogeneous results and the most recent hypothesis suggests that cardiac myxoma originates from a primitive pluripotential cardiogenic cell. We investigated the expressi...

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Bibliographic Details
Published in:The Journal of pathology 2006-06, Vol.209 (2), p.231-239
Main Authors: Orlandi, A, Ciucci, A, Ferlosio, A, Genta, R, Spagnoli, LG, Gabbiani, G
Format: Article
Language:English
Subjects:
actin isoforms
Actins - analysis
Adult
Aged
Aged, 80 and over
alpha smooth muscle actin
alpha smooth muscle actin, actin isoforms
Antigens, CD34 - analysis
Biological and medical sciences
Biomarkers, Tumor - analysis
cardiac myxoma
cardiac stem cells
cardiac tumours
CD34
Cells, Cultured
Endothelium, Vascular - chemistry
Female
Heart Neoplasms - pathology
Heart Neoplasms - ultrastructure
Humans
Immunohistochemistry - methods
Investigative techniques, diagnostic techniques (general aspects)
Male
Medical sciences
Microscopy, Confocal - methods
Microscopy, Electron - methods
Middle Aged
Muscle, Smooth, Vascular - chemistry
Myxoma - pathology
Myxoma - ultrastructure
Neoplasm Proteins - analysis
Neoplastic Stem Cells - pathology
Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques
Phenotype
phenotypic heterogeneity
Reverse Transcriptase Polymerase Chain Reaction - methods
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Summary:The origin of myxoma, the most frequent tumour of the heart, remains uncertain. Previous phenotypic characterizations have shown heterogeneous results and the most recent hypothesis suggests that cardiac myxoma originates from a primitive pluripotential cardiogenic cell. We investigated the expression of actin isoforms in 30 left atrial myxomas by immunohistochemistry and in eight consecutive tumours by RT‐PCR. α‐Smooth muscle actin (α‐SMA) protein and/or transcripts were detected in all cases, whereas α‐cardiac actin was observed in few cases and α‐skeletal actin was always absent. Besides classical features, vessel‐like structures were characterized by cells expressing CD34 and, less frequently, α‐SMA. Confocal microscopy showed focal co‐expression of CD34 and α‐SMA in myxoma cells, suggesting a gradual loss of stem endothelial markers and the acquisition of myocytic antigens. In order to confirm this hypothesis, early cardiac differentiation markers were also investigated. RT‐PCR documented the presence of transcripts for Sox9 (100%), Notch1 (87.5%), NFATc1 (37.5%), Smad6, metalloproteinases 1 and 2 alone or in variable combinations and the absence of ErbB3 and WT1. Myxoma cells maintained phenotypic heterogeneity in vitro, including the expression of α‐SMA and the presence of stress fibres. These findings document in cardiac myxoma cells phenotypic markers of the embryonic endothelial‐to‐mesenchymal transformation that precedes terminal differentiation of endocardial cushions, supporting the hypothesis that cardiac myxoma cells may derive from adult developmental remnants. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
ISSN:0022-3417
1096-9896
DOI:10.1002/path.1959