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Virchows Archiv
Published in: Virchows Archiv 2/2013

Open Access 01-02-2013 | Original Article

Sample parameters affecting the clinical relevance of RNA biomarkers in translational breast cancer research

Authors: Vassiliki Kotoula, Konstantine T. Kalogeras, George Kouvatseas, Despoina Televantou, Ralf Kronenwett, Ralph M. Wirtz, George Fountzilas

Published in: Virchows Archiv | Issue 2/2013

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Abstract

In the frame of translational breast cancer research, eligibility criteria for formalin-fixed paraffin-embedded tissue (FFPE) material processing for gene expression studies include tumor cell content (TCC) and sample site (primary vs metastatic tumors). Herein we asked whether the observed differences in gene expression between paired samples with respect to TCC and sample site also have different clinical significance. We assessed ESR1, ERBB2, MAPT, MMP7, and RACGAP1 mRNA expression with real time PCR in paired samples before (NMD) and after macrodissection (MD) from 98 primary tumors (PMD, PNMD) and 72 metastatic lymph nodes (LNMD, LNNMD), as well as from 93 matched P (mP) and LN (mLN). TCC range was 2.5–75 % in the NMD series and 28–98 % in the MD and in the mP/mLN series. The prognostic effect of these markers, individually or in clusters, remained stable between paired PMD/NMD. In comparison, cluster classification failed in the LNNMD group with lower TCC. In the mP/mLN cohort, RACGAP1 mRNA expression was of prognostic significance when tested in mLN samples (p < 0.001). Similarly, luminal B, HER2, and triple negative tumors were of dismal prognosis when classified in the LN component of the same series (mLN, overall survival: p = 0.013, p = 0.034, and p = 0.007, respectively). In conclusion, the clinical relevance of the RNA markers examined may be affected by TCC in metastatic LN samples but not in primary tumors, while it differs between primary tumors and matched metastases. These data will facilitate the design of translational studies involving FFPE sample series.
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Metadata
Title
Sample parameters affecting the clinical relevance of RNA biomarkers in translational breast cancer research
Authors
Vassiliki Kotoula
Konstantine T. Kalogeras
George Kouvatseas
Despoina Televantou
Ralf Kronenwett
Ralph M. Wirtz
George Fountzilas
Publication date
01-02-2013
Publisher
Springer-Verlag
Published in
Virchows Archiv / Issue 2/2013
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-012-1357-1

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