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Open Access 01-12-2018 | Research

Limited utility of tissue micro-arrays in detecting intra-tumoral heterogeneity in stem cell characteristics and tumor progression markers in breast cancer

Authors: Pascale Kündig, Charlotte Giesen, Hartland Jackson, Bernd Bodenmiller, Bärbel Papassotirolopus, Sandra Nicole Freiberger, Catharine Aquino, Lennart Opitz, Zsuzsanna Varga

Published in: Journal of Translational Medicine | Issue 1/2018

Abstract

Background

Intra-tumoral heterogeneity has been recently addressed in different types of cancer, including breast cancer. A concept describing the origin of intra-tumoral heterogeneity is the cancer stem-cell hypothesis, proposing the existence of cancer stem cells that can self-renew limitlessly and therefore lead to tumor progression. Clonal evolution in accumulated single cell genomic alterations is a further possible explanation in carcinogenesis. In this study, we addressed the question whether intra-tumoral heterogeneity can be reliably detected in tissue-micro-arrays in breast cancer by comparing expression levels of conventional predictive/prognostic tumor markers, tumor progression markers and stem cell markers between central and peripheral tumor areas.

Methods

We analyzed immunohistochemical expression and/or gene amplification status of conventional prognostic tumor markers (ER, PR, HER2, CK5/6), tumor progression markers (PTEN, PIK3CA, p53, Ki-67) and stem cell markers (mTOR, SOX2, SOX9, SOX10, SLUG, CD44, CD24, TWIST) in 372 tissue-micro-array samples from 72 breast cancer patients. Expression levels were compared between central and peripheral tumor tissue areas and were correlated to histopathological grading. 15 selected cases additionally underwent RNA sequencing for transcriptome analysis.

Results

No significant difference in any of the analyzed between central and peripheral tumor areas was seen with any of the analyzed methods/or results that showed difference. Except mTOR, PIK3CA and SOX9 (nuclear) protein expression, all markers correlated significantly (p < 0.05) with histopathological grading both in central and peripheral areas.

Conclusion

Our results suggest that intra-tumoral heterogeneity of stem-cell and tumor-progression markers cannot be reliably addressed in tissue-micro-array samples in breast cancer. However, most markers correlated strongly with histopathological grading confirming prognostic information as expression profiles were independent on the site of the biopsy was taken.

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Title: Limited utility of tissue micro-arrays in detecting intra-tumoral heterogeneity in stem cell characteristics and tumor progression markers in breast cancer
Authors: Pascale Kündig
Charlotte Giesen
Hartland Jackson
Bernd Bodenmiller
Bärbel Papassotirolopus
Sandra Nicole Freiberger
Catharine Aquino
Lennart Opitz
Zsuzsanna Varga
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Journal of Translational Medicine / Issue 1/2018
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/s12967-018-1495-6

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