Slachmuylders E, Laenen A, Vernemmen A, Keupers M, Nevelsteen I, Han S N, Neven P, Van Ongeval C, Wildiers H, Smeets A, Floris G
Department of Imaging and Pathology, Laboratory of Translational Cell and Tissue Research, KU Leuven - University of Leuven, Leuven, Belgium.
Department of Pathology, University Hospitals Leuven, KU Leuven - University of Leuven, Leuven, Belgium.
APMIS. 2025 Jan;133(1):e13485. doi: 10.1111/apm.13485. Epub 2024 Oct 25.
Phyllodes tumors (PTs) are rare breast tumors showing overlapping features with fibroadenomas (FAs). Diagnosis on small biopsies is challenging. New diagnostic markers are needed. Here we evaluated immunohistochemical staining of histone 3 trimethyl-lysine-27 (H3K27me3) as a diagnostic and prognostic marker in a series of PTs. Surgically removed PTs at our institution (September 1990 and July 2022) and control FAs. Tissue micro-arrays (4 cores, 2 mm Ø) stained with H3K27me3, and scored with QuPath-derived H-score. Fisher exact test, Mann-Whitney U-test and chi-squared test used for group comparison. ROC analysis applied to define cutoffs. Cox proportional hazards models were used for assessing disease-free survival (DFS), overall survival (OS), and disease-specific survival (DSS) in PTs. We included 81 patients with PTs and 44 patients with FAs. QuPath-derived H-scores of stromal H3K27me3 were statically significantly lower in PTs than in FAs (p < 0.001). We identified exploratory cutoffs to discriminate FAs from benign and malignant PTs (AUC = 0.78 and 0.73, respectively). No associations between DFS, OS, or DSS and H3K27me3 expression were found. H3K27me3 expression differs between FAs and PTs, indicating potential as diagnostic marker, but it is not predictive for DFS, OS or DSS in PTs. Further validation is needed.
叶状肿瘤（PTs）是一种罕见的乳腺肿瘤，具有与纤维腺瘤（FAs）重叠的特征。对小活检标本进行诊断具有挑战性。需要新的诊断标志物。在此，我们评估了组蛋白3三甲基赖氨酸-27（H3K27me3）的免疫组化染色作为一系列PTs的诊断和预后标志物。收集了我们机构在1990年9月至2022年7月期间手术切除的PTs以及对照FAs。用H3K27me3对组织微阵列（4个芯，直径2毫米）进行染色，并用QuPath衍生的H评分进行评分。采用Fisher精确检验、Mann-Whitney U检验和卡方检验进行组间比较。应用ROC分析来确定临界值。采用Cox比例风险模型评估PTs的无病生存期（DFS）、总生存期（OS）和疾病特异性生存期（DSS）。我们纳入了81例PTs患者和44例FAs患者。PTs中基质H3K27me3的QuPath衍生H评分在统计学上显著低于FAs（p < 0.001）。我们确定了探索性临界值以区分FAs与良性和恶性PTs（AUC分别为0.78和0.73）。未发现DFS、OS或DSS与H3K27me3表达之间存在关联。FAs和PTs之间的H3K27me3表达存在差异，表明其具有作为诊断标志物的潜力，但它不能预测PTs的DFS、OS或DSS。需要进一步验证。
