Schandiz Hossein, Farkas Lorant, Park Daehoon, Liu Yan, Andersen Solveig N, Sauer Torill, Geisler Jürgen
Department of Oncology, Akershus University Hospital (AHUS), Lørenskog, Norway.
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Front Oncol. 2025 Jan 28;15:1467664. doi: 10.3389/fonc.2025.1467664. eCollection 2025.
We investigated the role of Ki67, a ubiquitous marker in cancer, within the context of ductal carcinoma (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 DCIS, 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.
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 (DCIS) remains uncertain. We studied Ki67 immunohistochemistry interobserver diagnostic agreement at different cutoff values in high-grade 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 HER2, LumB HER2, HER2-enriched, and triple-negative)).
Using histopathological specimens from 484 patients diagnosed with DCIS between 1996 and 2018, we implemented the 2013 St. Gallen recommendations for surrogate immunomolecular subtyping of IBC. Subtypes were classified, and the Ki67 interobserver diagnostic agreement between Counting Pathologist 1 (CP1) and CP2 was calculated using Cohen's kappa coefficient at various cutoff values.
The Cohen's kappa coefficient for interobserver agreement between CP1 and CP2 was κ = 0.586, indicating moderate agreement. Ki67 levels varied significantly among subtypes ( < 0.0001), with a median Ki67% being higher in cases with invasive components ( = 0.0351). Low PR combined with high Ki67% was significantly associated with HER2 overexpression ( = 0.0107).
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 overexpression, showing possible clinical implications for identifying high-risk DCIS.
摘要：我们在浸润性乳腺癌的前体导管原位癌（DCIS）的背景下，研究了癌症中普遍存在的标志物Ki67的作用。通过对大量队列的组织病理学和免疫病理学样本进行严格分析，本研究揭示了Ki67表达升高、孕激素（PR）水平降低和HER2过表达之间的密切相关性，这表明DCIS具有侵袭性表型。这些发现为DCIS的替代免疫分子亚型格局提供了新的见解，可能会优化风险分层和治疗方法。这一阐释强调了Ki67作为DCIS中预后和预测生物标志物的转化意义，对个性化治疗模式和患者预后具有重要意义。
背景：Ki67增殖指数广泛应用于包括浸润性乳腺癌（IBC）在内的各种肿瘤。然而，其预后效用常常受到技术复杂性的限制。其在导管原位癌（DCIS）中的诊断和临床意义仍不确定。我们研究了在高级别DCIS中不同临界值下Ki67免疫组化的观察者间诊断一致性。此外，我们还研究了高级别DCIS中各种亚型（腔面（Lum）A、LumB HER2、LumB HER2、HER2富集型和三阴性）中Ki67表达、PR水平和人表皮生长因子受体2（HER2）之间的关联。
方法：我们使用了1996年至2018年间诊断为DCIS的484例患者的组织病理学标本，实施了2013年圣加仑关于IBC替代免疫分子亚型分类的建议。对亚型进行分类，并使用Cohen's kappa系数计算计数病理学家1（CP1）和CP2之间在不同临界值下的Ki67观察者间诊断一致性。
结果：CP1和CP2之间观察者间一致性的Cohen's kappa系数为κ = 0. 586，表明一致性中等。Ki67水平在各亚型之间存在显著差异（< 0.0001），有侵袭成分的病例中Ki67%的中位数更高（= 0.0351）。低PR与高Ki67%显著相关与HER2过表达相关（= 0.0107）。
结论：Ki67计数的观察者间一致性中等。Ki67表达在高级别DCIS中表现出相当大的变异性。低PR水平与高Ki67表达与HER2过表达相关，这对识别高危DCIS可能具有临床意义。
