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Morphological intratumor heterogeneity in ductal carcinoma in situ of the breast

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Abstract

Ductal carcinoma in situ (DCIS) of the breast is a heterogeneous disease in terms of morphological characteristics, protein expression profiles, genetic abnormalities, and potential for progression. Molecular heterogeneity has been extensively studied in DCIS. Yet morphological heterogeneity remains relatively undefined. This study investigated morphological intratumor heterogeneity in a series of 51 large DCIS. Nuclear atypia, DCIS architecture, necrosis, calcifications, stromal architecture, and stromal inflammation were assessed in one biopsy slide and three representative slides from each corresponding resection. For each histopathological feature, a histo-score was determined per slide and compared between the biopsy and the resection, as well as within a single resection. Statistical analysis comprised of Friedman tests, post hoc Wilcoxon tests with Bonferroni corrections, Mann-Whitney U tests, and chi-square tests. Despite substantial morphological heterogeneity in around 50% of DCIS, the histopathological assessment of the biopsy did not statistically significantly differ from the resection. Morphological heterogeneity was not significantly associated with patient age, DCIS size, or type of surgery, except for a weak association between heterogeneous stromal inflammation and smaller DCIS size. At the group level, the degree of heterogeneity did not significantly affect the representativity of a biopsy. At the individual patient level, however, the presence of necrosis, intraductal calcifications, myxoid stromal changes, and high-grade nuclear atypia was underestimated in a minority of DCIS patients. This study confirms the presence of morphological heterogeneity in DCIS for all six evaluated histopathological features. This should be kept in mind when taking biopsy-based treatment decisions for DCIS patients.

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Data availability

All data concerning this study can be obtained from the corresponding author upon reasonable request.

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Acknowledgments

The authors gratefully acknowledge the help of all lab technicians of the Departments of Pathology of the CHU UCL Namur and the Cliniques universitaires Saint-Luc.

Funding

MR Van Bockstal received a postdoctoral clinical mandate (2019-089) from the not-for-profit organization “Foundation Against Cancer” (Brussels, Belgium).

MR Van Bockstal and C Galant are funded by the “Fonds Gaëtan Lagneaux” (Fondation Saint-Luc, Brussels, Belgium).

FP Duhoux received a postdoctoral clinical mandate (2017-034) from the not-for-profit organization “Foundation Against Cancer” (Brussels, Belgium).

Author information

Authors and Affiliations

  1. Department of Pathology, CHU UCL Namur, Site Godinne, Avenue Docteur G. Thérasse 1, 5530, Yvoir, Belgium

    Claudia Stanciu-Pop & Marie-Cécile Nollevaux

  2. Breast Clinic, King Albert II Cancer Institute, Cliniques universitaires Saint-Luc, Avenue Hippocrate 10, 1200, Brussels, Belgium

    Martine Berlière, Francois P. Duhoux, Christine Galant & Mieke R. Van Bockstal

  3. Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Avenue Hippocrate 10, 1200, Brussels, Belgium

    Martine Berlière, Francois P. Duhoux, Latifa Fellah, Christine Galant & Mieke R. Van Bockstal

  4. Department of Medical Oncology, King Albert II Cancer Institute, Cliniques universitaires Saint-Luc, Avenue Hippocrate 10, 1200, Brussels, Belgium

    Francois P. Duhoux

  5. Department of Radiology, Cliniques universitaires Saint-Luc, Avenue Hippocrate 10, 1200, Brussels, Belgium

    Latifa Fellah

  6. Department of Pathology, Cliniques universitaires Saint-Luc, Avenue Hippocrate 10, 1200, Brussels, Belgium

    Christine Galant & Mieke R. Van Bockstal

Authors
  1. Claudia Stanciu-Pop
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  2. Marie-Cécile Nollevaux
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  3. Martine Berlière
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  4. Francois P. Duhoux
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  7. Mieke R. Van Bockstal
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Contributions

• CSP: Data curation, methodology, formal analysis, visualization, project administration, writing of the original draft

• MCN: Data curation, methodology, project administration, writing – review and editing

• MB: Methodology, resources, writing – review and editing

• FPD: Methodology, resources, writing – review and editing

• LF: Methodology, resources, writing – review and editing

• CG: Data curation, methodology, project administration, supervision, writing – review and editing

• MRVB: Conceptualization, data curation, formal analysis, methodology, visualization, writing – review and editing

Corresponding author

Correspondence to Mieke R. Van Bockstal.

Ethics declarations

This study was approved by the Ethics Committee (RETRO-DCIS-13/2019/25JUI/276) of the Cliniques universitaires Saint-Luc (Brussels, Belgium). This study was performed in accordance with the World Medical Association’s Helsinki Declaration for Human Studies.

Conflict of interest

The authors declare that they have no conflict of interest.

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Reports of preliminary data:

• The data reported in this manuscript have partially been presented during the virtual ESMO Breast Cancer meeting (May 2020), and the corresponding abstract has been published in Annals of Oncology.

• The data of this original article were presented as a poster during the virtual 32nd ESP Conference (December 2020).

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Stanciu-Pop, C., Nollevaux, MC., Berlière, M. et al. Morphological intratumor heterogeneity in ductal carcinoma in situ of the breast. Virchows Arch 479, 33–43 (2021). https://doi.org/10.1007/s00428-021-03040-6

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