Department of Pathology, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, 518033 Shenzhen, China.
Department of Pathology, The Second People's Hospital of Shenzhen, 518000 Shenzhen, China.
Ann Diagn Pathol. 2023 Oct;66:152176. doi: 10.1016/j.anndiagpath.2023.152176. Epub 2023 Jul 4.
Phyllodes tumors (PTs) are biphasic fibroepithelial lesions that occur in the breast. Diagnosing and grading PTs remains a challenge in a small proportion of cases, due to the lack of reliable specific biomarkers. We screened a potential marker versican core protein (VCAN) through microproteomics analysis, validated its role for the grading of PTs by immunohistochemistry, and analyzed the correlation between VCAN expression and clinicopathological characteristics. Cytoplasmic immunoreactivity for VCAN was identified in all benign PT samples, among which 40 (93.0 %) showed VCAN-positive staining in ≥50 % of tumor cells. Eight (21.6 %) borderline PT samples showed VCAN-positive staining in ≥50 % of the cells with weak to moderate staining intensity, whereas 29 samples (78.4 %) showed VCAN-positive staining in <50 % of the cells. In malignant PTs, 16 (84.2 %) and three (15.8 %) samples showed VCAN-positive staining in <5 % and 5-25 % of stromal cells, respectively. Fibroadenomas showed a similar expression pattern to benign PTs. Fisher's exact test showed that the percentages of positive cells (P < .001) and staining intensities (P < .001) of tumor cells were significantly different between the five groups. VCAN positivity was associated with tumor categories (P < .0001) and CD34 expression (P < .0001). The expression of VCAN gradually decreases as the tumor categories increases, following recurrence. To the best of our knowledge, our results are the first in the literature to reveal that VCAN is useful for diagnosing and grading PTs. The expression level of VCAN appeared to be negatively associated with PT categories, suggesting that dysregulation of VCAN may be involved in the tumor progression of PTs.
叶状肿瘤（PTs）是一种发生在乳房中的双相纤维上皮性病变。由于缺乏可靠的特异性生物标志物，一小部分病例的诊断和分级仍然具有挑战性。我们通过微蛋白质组学分析筛选了一个潜在的标志物核心蛋白聚糖（VCAN），通过免疫组织化学验证了其在 PT 分级中的作用，并分析了 VCAN 表达与临床病理特征的相关性。所有良性 PT 样本的细胞质中均检测到 VCAN 的免疫反应性，其中 40 例（93.0%）肿瘤细胞中≥50%的细胞显示 VCAN 阳性染色。8 例（21.6%）交界性 PT 样本中≥50%的细胞显示弱阳性至中度染色强度的 VCAN 阳性染色，而 29 例（78.4%）样本中<50%的细胞显示 VCAN 阳性染色。在恶性 PT 中，16 例（84.2%）和 3 例（15.8%）样本中分别有<5%和 5-25%的基质细胞显示 VCAN 阳性染色。纤维腺瘤的表达模式与良性 PT 相似。Fisher 精确检验显示，五组之间肿瘤细胞阳性细胞百分比（P<0.001）和染色强度（P<0.001）均有显著差异。VCAN 阳性与肿瘤类型（P<0.0001）和 CD34 表达（P<0.0001）有关。随着肿瘤类型的增加，VCAN 的表达逐渐降低，且与复发相关。据我们所知，我们的结果是文献中首次揭示 VCAN 对诊断和分级 PT 有用。VCAN 的表达水平似乎与 PT 类型呈负相关，提示 VCAN 失调可能参与了 PT 的肿瘤进展。
