Tang Ping, Wang Xi, Schiffhauer Linda, Wang Jianmin, Bourne Patricia, Yang Qi, Quinn Andrew, Hajdu Steven I
Department of Pathology and Laboratory Medicine, University of Rochester Medical Center Box 626, 601 Elmwood Ave, Rochester, NY 14642, USA.
Ann Clin Lab Sci. 2006 Winter;36(1):16-22.
Ductal carcinoma in situ (DCIS) is a group of heterogeneous lesions genetically, morphologically, and biologically. Recently, breast epithelium in the terminal ductal lobular unit has been sub-classified based on the expression of several cytokeratin markers as stem cells (CK5/6 +), luminal cells (CK8, CK18 +), and basal cells (CK14, CK17 +). In this study we describe the relationship between DCIS of different nuclear grades (non-high grade and high grade) and these cell origin markers. Fifty-three cases of non-high grade and 46 cases of high grade DCIS were selected, and representative sections from each case were stained with antibodies to these cytokeratin markers. High grade DCIS showed significantly higher rates of expression with stem and basal cell markers compared with non-high grade DCIS (p <0.05). The majority of DCIS, both high grade and non-high grade, expressed luminal cell markers (67% to 91%) and single type of cell origin marker (72% to 87%). High-grade DCIS more frequently co-expressed all three types of cell origin markers compared with non-high grade DCIS (p <0.05). In summary, a subset of high grade DCIS frequently rises from stem or/and basal cell populations; the subset is associated with poor prognosis in invasive breast carcinoma. Thus, these markers may be used to identify a potentially more aggressive subgroup of breast carcinoma at its pre-invasive stage (DCIS), and to manage it accordingly. Second, most DCIS express luminal cell markers, suggesting that malignant transformation occurs relatively late along the cell differentiation pathway, contrary to the traditional belief that most neoplasms arise from a more primitive stem cell population. Third, the majority of DCIS exclusively express one type of progenitor marker, indicating that in most incidences they may arise from a single progenitor population. Last, triple expression of all types of cell origin marker is frequently associated with high grade DCIS, suggesting that more complicated pathways are involved in these more aggressive lesions. Further studies are needed to delineate the relationships of cell origin markers in DCIS and invasive carcinoma to the clinical outcome.
导管原位癌（DCIS）在基因、形态和生物学方面是一组异质性病变。最近，终末导管小叶单位中的乳腺上皮已根据几种细胞角蛋白标记物的表达被分类为干细胞（CK5/6+）、管腔细胞（CK8、CK18+）和基底细胞（CK14、CK17+）。在本研究中，我们描述了不同核级别的DCIS（非高级别和高级别）与这些细胞起源标记物之间的关系。选取了53例非高级别DCIS和46例高级别DCIS病例，并对每个病例的代表性切片用这些细胞角蛋白标记物的抗体进行染色。与非高级别DCIS相比，高级别DCIS显示出干细胞和基底细胞标记物的表达率显著更高（p<0.05）。大多数DCIS，无论是高级别还是非高级别，都表达管腔细胞标记物（67%至91%）和单一类型的细胞起源标记物（72%至87%）。与非高级别DCIS相比，高级别DCIS更频繁地共表达所有三种类型的细胞起源标记物（p<0.05）。总之，一部分高级别DCIS经常起源于干细胞或/和基底细胞群体；该亚组与浸润性乳腺癌的不良预后相关。因此，这些标记物可用于在其浸润前阶段（DCIS）识别潜在更具侵袭性的乳腺癌亚组，并据此进行管理。其次，大多数DCIS表达管腔细胞标记物，这表明恶性转化在细胞分化途径中发生得相对较晚，这与传统观点认为大多数肿瘤起源于更原始的干细胞群体相反。第三，大多数DCIS仅表达一种类型的祖细胞标记物，这表明在大多数情况下它们可能起源于单个祖细胞群体。最后，所有类型细胞起源标记物的三重表达经常与高级别DCIS相关，这表明这些更具侵袭性的病变涉及更复杂的途径。需要进一步研究来阐明DCIS和浸润性癌中细胞起源标记物与临床结果之间的关系。
