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. 2013 Dec 18;8(12):e84189.
doi: 10.1371/journal.pone.0084189. eCollection 2013.

ESR1 amplification in breast cancer by optimized RNase FISH: frequent but low-level and heterogeneous

Cathy B Moelans  1 , Frederik Holst  2 , Olaf Hellwinkel  3 , Ronald Simon  4 , Paul J van Diest  1
Affiliations

ESR1 amplification in breast cancer by optimized RNase FISH: frequent but low-level and heterogeneous

Cathy B Moelans et al. PLoS One. .

Abstract

Prevalence of ESR1 amplification in breast cancer is highly disputed and discrepancies have been related to different technical protocols and different scoring approaches. In addition, pre-mRNA artifacts have been proposed to influence outcome of ESR1 FISH analysis. We analyzed ESR1 gene copy number status combining an improved RNase FISH protocol with multiplex ligation-dependent probe amplification (MLPA) after laser microdissection. FISH showed a high prevalence of ESR1 gains and amplifications despite RNase treatment but MLPA did not confirm ESR1 copy number increases detected by FISH in more than half of cases. We suggest that the combination of the ESR1-specific intra-tumor heterogeneity and low-level copy number increase accounts for these discrepancies.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Effect of RNase treatment on FISH and on correlation between FISH and MLPA.
(a) RNase pretreatment resulted in a higher fraction of tumor cells showing point-shaped FISH signals, by eliminating eye catching fuzzy clusters of ESR1 signals seen by standard FISH (b) MLPA copy number ratios in FISH “not increased”, gained and amplified samples without and with RNase treatment.
See this image and copyright information in PMC

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