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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Breast Cancer
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1467664

High Ki67 Expression, HER2 overexpression, and Low Progesterone Receptors Levels in High-Grade DCIS: Significant Associations with Clinical Practice Implications

Provisionally accepted
Hossein Schandiz Hossein Schandiz 1,2*Lorant Farkas Lorant Farkas 1,3Daehoon Park Daehoon Park 3Yan Liu Yan Liu 1,2Solveig N. Andersen Solveig N. Andersen 1Torill Sauer Torill Sauer 1Jürgen Geisler Jürgen Geisler 1,2
  • 1 University of Oslo, Oslo, Oslo, Norway
  • 2 Akershus University Hospital, Lørenskog, Norway
  • 3 Oslo University Hospital, Oslo, Nordland, Norway

The final, formatted version of the article will be published soon.

    We investigated the role of Ki67, a ubiquitous marker in cancer, within the context of ductal carcinoma in situ (DCIS), a precursor of invasive breast cancer. Through rigorous analysis of histopathological and immunopathological samples from a substantial cohort, this study revealed robust correlations between heightened Ki67 expression, diminished progesterone (PR) levels, and HER2 overexpression, indicative of aggressive DCIS phenotypes. These findings offer novel insights into the surrogate immunomolecular subtyping landscape of early-stage breast cancer, potentially refining risk stratification and therapeutic approaches. This elucidation underscores the translational significance of Ki67 as a prognostic and predictive biomarker in DCIS, with implications for personalized treatment paradigms and patient outcomes.Background: The Ki67 proliferation index is widely used in various tumors, including invasive breast carcinoma (IBC). However, its prognostic utility is often constrained by technical complexity. Its diagnostic and clinical significance in ductal carcinoma in situ (DCIS) remains uncertain. We studied Ki67 immunohistochemistry interobserver diagnostic agreement at different cutoff values in highgrade DCIS. Additionally, we investigated the associations between Ki67 expression, PR levels, and human epidermal growth factor receptor 2 (HER2) in high-grade DCIS among various subtypes (Luminal (Lum) A, LumB HER2ˉ, LumB HER2 + , HER2-enriched, and triple-negative)). Methods: Using histopathological specimens from 494 patients diagnosed with DCIS between 1996 and 2018, we implemented the 2013 St. Gallen recommendations for surrogate immunomolecular subtyping of IBC.Pathologist 1 (CP1) and CP2 was calculated using Cohen's kappa coefficient when we used the 20% cutoff. Results: The Cohen's kappa coefficient for interobserver agreement between CP1 and CP2 was ƙ = 0.586, indicating moderate agreement. Ki67 levels varied significantly among subtypes (p < 0.0001), with a median Ki67% being higher in cases with invasive components (p = 0.0351). Low PR combined with high Ki67% was significantly associated with HER2 overexpression (p = 0.0107). Conclusions:Interobserver agreement for the Ki67 count was moderate. Ki67 expression showed considerable variability in high-grade DCIS. Low PR levels combined with high Ki67 expression were linked to HER2-enriched subtype and HER2 overexpression, showing possible clinical implications for identifying high-risk DCIS.

    Keywords: Ductal carcinoma in situ (DCIS) of the breast, immunohistochemisty, Personalized medicine (PM), Ki67 proliferation index, Human Epidermal Growth Factor Receptor 2 (HER2)

    Received: 20 Jul 2024; Accepted: 02 Jan 2025.

    Copyright: © 2025 Schandiz, Farkas, Park, Liu, Andersen, Sauer and Geisler. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Hossein Schandiz, University of Oslo, Oslo, 0316, Oslo, Norway

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