Research Papers: Pathology:

Stromal expression of ALDH1 in human breast carcinomas indicates reduced tumor progression

Natalia Bednarz-Knoll _, Paulina Nastały, Anna Żaczek, Małgorzata Stoupiec, Sabine Riethdorf, Harriet Wikman, Volkmar Müller, Jarosław Skokowski, Jolanta Szade, Aleksandra Sejda, Marzena Wełnicka-Jaśkiewicz and Klaus Pantel

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Oncotarget. 2015; 6:26789-26803. https://doi.org/10.18632/oncotarget.4628

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Natalia Bednarz-Knoll1, Paulina Nastały1, Anna Żaczek2, Małgorzata Stoupiec1, Sabine Riethdorf1, Harriet Wikman1, Volkmar Müller3, Jarosław Skokowski4,5, Jolanta Szade6, Aleksandra Sejda6, Marzena Wełnicka-Jaśkiewicz7, Klaus Pantel1

1Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Laboratory of Cell Biology, Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk, Poland

3Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

4Bank of Frozen Tissues & Genetic Specimens, Medical University of Gdańsk, Gdańsk, Poland

5Department of Surgical Oncology, Medical University of Gdańsk, Gdańsk, Poland

6Department of Pathomorphology, Medical University of Gdańsk, Gdańsk, Poland

7Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland

Correspondence to:

Natalia Bednarz-Knoll, e-mail: [email protected]

Keywords: breast cancer, ALDH1, intra-tumoral stroma, tumor-stroma interactions, tumor progression

Received: February 24, 2015     Accepted: July 06, 2015     Published: July 20, 2015


Interactions between cancer cells and microenvironment are emerging issue in tumor progression. Aldehyde dehydrogenase 1 (ALDH1) is a recognized cancer stem cell marker but little is known about its role in intratumoral stroma. Therefore, we focused on ALDH1 expression in tumor-associated stroma of breast carcinomas (BrCa).

Stromal and tumoral ALDH1 expression was evaluated immunohistochemically in BrCa and their lymph node metastases (LNMs), and related to clinico-pathological characteristics, patients’ outcome, presence of CD68, HLADR, retinoic acid (RA) in stroma, and selected proteins in tumor cells.

ALDH1(+) stromal cells were detected in 53% of 374 BrCa and 61% of 102 LNMs. ALDH1(+) stroma in primary tumor correlated to longer disease-free (p = 0.030), metastasis-free (p = 0.024), and overall survival (p = 0.043) having an independent prognostic impact on DFS (multivariate analysis, p = 0.047). It was associated with concomitant presence of HLA-DR(+) stromal cells and RA in tumor cells (both p < 0.001), and inversely associated with vimentin expression in tumor cells (p = 0.036). ALDH1(+) stroma in LNMs correlated inversely to presence of disseminated tumor cells in patients’ bone marrow (p = 0.014) and was independent prognosticator of shorter DFS and MFS (multivariate analysis, p = 0.004 and p = 0.002, respectively).

In conclusion, ALDH1 expression in tumor-associated stromal cells indicates reduced BrCa progression, possibly via RA secretion.

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