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. 2024 Apr;309(4):1525-1533.
doi: 10.1007/s00404-023-07225-z. Epub 2023 Oct 30.

Determination of the androgen receptor status of disseminated tumor cells in primary breast cancer patients

Natalia Krawczyk #  1 , Bernadette Jaeger #  2 , Piperek-Jäger Martina  1 , Lopez-Cotarelo Rodriguez-Noriega Cristina  3 , Neubacher Melissa  1 , Banys-Paluchowski Maggie  4 , Meier-Stiegen Franziska  1 , Neubauer Hans  1 , Niederacher Dieter  1 , Ruckhäberle Eugen  1 , Mohrmann Svjetlana  1 , Hoffmann Jürgen  1 , Kaleta Thomas  1 , Esposito Irene  3 , Fehm Tanja  1
Affiliations

Determination of the androgen receptor status of disseminated tumor cells in primary breast cancer patients

Natalia Krawczyk et al. Arch Gynecol Obstet. 2024 Apr.

Abstract

Purpose: Androgen receptor (AR) can serve as a new therapeutic target since it was shown to play a proliferative role in several breast cancer (BC) subtypes. Moreover, AR positivity has been suggested to reflect the metastatic potential of tumor cells in some BC subtypes. The aim of this study was to determine the AR expression on disseminated tumor cells (DTCs) as a surrogate marker of minimal residual disease (MRD) and potential precursor of metastasis in early BC.

Methods: Bone marrow (BM) aspirates from 62 DTC-positive early BC patients were included into this study and analyzed by immunofluorescence staining for the presence of AR-positive DTCs. CK-positive, CD45-negative cells containing an intact nucleus (DAPI positive) were identified as DTCs. AR expression of the primary tumor (PT) was assessed by immunohistochemistry on formalin-fixed, paraffin-embedded (FFPE) tumor sections from core biopsies and surgical specimens.

Results: AR status of DTCs could be determined in 21 patients. We detected AR-positive DTCs in nine samples (43%). AR expression of DTCs and corresponding PT showed a concordance rate of 33%. The DTC-AR status did not correlate with clinicopathological factors, nor did we observe a significant correlation between the AR status of the PT and other established prognostic factors for BC.

Conclusion: AR-positive DTCs can be detected in BM of early BC patients with a marked discordance of the AR status between DTCs and corresponding PTs. The clinical significance of these findings needs further investigation.

Keywords: Minimal residual disease; Predictive marker; Targeted therapy.

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Conflict of interest statement

The authors declare that there are no conflicts of interest.

Figures

Fig. 1
Fig. 1
Study flow chart. DTC: disseminated tumor cell, AB: antibody, IF: immunofluorescence
Fig. 2
Fig. 2
Androgen receptor (AR) control stainings: A LNCaP prostate cancer cell line (positive control), B Du145 prostate cancer cell line (negative control), C AR isotype control staining (LNCaP), D CD45 positive control staining (leucocyte)
Fig. 3
Fig. 3
Androgen receptor (AR) staining of DTCs in primary breast cancer patients: a AR-positive staining. b AR-negative staining
See this image and copyright information in PMC

References

    1. Prescott J, Coetzee GA. Molecular chaperones throughout the life cycle of the androgen receptor. Cancer Lett. 2006;231(1):12–19. doi: 10.1016/j.canlet.2004.12.037. - DOI - PubMed
    1. Heemers HV, Tindall DJ. Androgen receptor (AR) coregulators: a diversity of functions converging on and regulating the AR transcriptional complex. Endocr Rev. 2007;28(7):778–808. doi: 10.1210/er.2007-0019. - DOI - PubMed
    1. Kumar R, McEwan IJ. Allosteric modulators of steroid hormone receptors: structural dynamics and gene regulation. Endocr Rev. 2012;33(2):271–299. doi: 10.1210/er.2011-1033. - DOI - PMC - PubMed
    1. Isola JJ. Immunohistochemical demonstration of androgen receptor in breast cancer and its relationship to other prognostic factors. J Pathol. 1993;170(1):31–35. doi: 10.1002/path.1711700106. - DOI - PubMed
    1. Brys M. Androgens and androgen receptor: do they play a role in breast cancer? Med Sci Monit. 2000;6(2):433–438. - PubMed

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