Kim Sun Il, Koo Ja Seung
Cancer Biomark. 2020;29(2):235-243. doi: 10.3233/CBM-191276.
Phyllodes tumor (PT) is a rare tumor showing various malignant potential. The histological grade of PT is related to clinical outcome, but its relationship between gaining of malignant potential and underlying mechanism including cancer stem cell factor was not understood yet.
The main purpose of this study was to determine the expression pattern of cancer stem cell marker in PT and to understand its clinical and pathological implications.
CD44, CD166, ALDH1, and Ki-67 immunohistochemistry were performed on a tissue microarray from 185 cases of PT specimens (138 benign, 32 borderline, 15 malignant). The immunohistochemistry result and clinicopathological parameter of each cases were compared to analyze the implications of cancer stem cell markers on PT.
Borderline/malignant PT showed higher CD44 expression of the stromal component than benign PT (p< 0.001). In lower histologic grade PT, CD166 showed increased expression in the epithelial component (p= 0.019), but decreased in the stromal component (p< 0.001). Stromal overgrowth was rarely observed as the number of positive cancer stem cell markers increased in the epithelial component (p< 0.001). In the stromal component, the number of positive cancer stem cell markers was related to higher histologic grade (p< 0.001), and increased stromal cellularity (p< 0.001), stromal atypia (p= 0.003), and stromal mitosis (p= 0.002). In benign PT, CD44 negativity (p= 0.013) and a decreased number of positive cancer stem cell markers (p= 0.012) in the epithelial component were related to poor prognosis.
The cancer stem cell markers, CD44 and CD166, are expressed in both the epithelial and stromal components of phyllodes tumor. Besides, ALDH1 is only expressed in stromal component. In the stromal component, expression of cancer stem cell markers increases with higher PT histologic grade. In the epithelial component, the absence of cancer stem cell marker expression is related to poor clinical prognosis.
叶状肿瘤（PT）是一种罕见的具有不同恶性潜能的肿瘤。PT的组织学分级与临床结局相关，但其恶性潜能获得与包括癌症干细胞因子在内的潜在机制之间的关系尚不清楚。
本研究的主要目的是确定癌症干细胞标志物在PT中的表达模式，并了解其临床和病理意义。
对185例PT标本（138例良性、32例交界性、15例恶性）的组织芯片进行CD44、CD166、ALDH1和Ki-67免疫组化检测。比较各病例的免疫组化结果和临床病理参数，分析癌症干细胞标志物对PT的影响。
交界性/恶性PT间质成分的CD44表达高于良性PT（p<0.001）。在组织学分级较低的PT中，CD166在上皮成分中表达增加（p=0.019），但在间质成分中表达降低（p<0.001）。随着上皮成分中癌症干细胞标志物阳性数量增加，间质过度生长很少见（p<0.001）。在间质成分中，癌症干细胞标志物阳性数量与较高的组织学分级相关（p<0.001），且与间质细胞增多（p<0.001）、间质异型性（p=0.003）和间质有丝分裂（p=0.002）增加有关。在良性PT中，上皮成分中CD44阴性（p=0.013）和癌症干细胞标志物阳性数量减少（p=0.012）与预后不良相关。
癌症干细胞标志物CD44和CD166在叶状肿瘤的上皮和间质成分中均有表达。此外，ALDH1仅在间质成分中表达。在间质成分中，癌症干细胞标志物的表达随PT组织学分级升高而增加。在上皮成分中，癌症干细胞标志物表达缺失与不良临床预后相关。
