Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype
Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype
复制标题
DOI：
10.1158/1078-0432.ccr-06-0169
复制
发表时间：
2006-10-01
影响因子：
11.5
通讯作者：
Cote, Richard J.
中科院分区：
文献类型：
--
作者：
Balic, Marija;Lin, Henry;Cote, Richard J.
目的：乳腺癌患者骨髓中存在播散性肿瘤细胞（DTC）是公认的独立预后因素。这些细胞的生物转移潜力尚未显示。在原发肿瘤和远处转移瘤中均显示存在推定的乳腺癌干细胞。这些具有CD 44（+）CD 24（-/低）表型的细胞代表了原发性乳腺癌中的少数群体，并与自我更新和致瘤潜力相关。认识到潜在的影响，假定的干细胞之间的DTC的患病率，我们评估了骨髓DTC.Experimental Design：我们采用了双/三染色免疫组化协议和修改建立的骨髓细胞角蛋白（CK）染色协议，通过添加额外的抗原，CD 44和/或CD 24的步骤。我们评估了50例早期乳腺癌患者的骨髓标本，这些标本先前被归类为CK+。通过光学显微镜、荧光显微镜和光谱成像检查CK+细胞的CD 44和CD 24表达。结果：我们在所有CK+标本中检测到了假定的干细胞样表型.与原发性肿瘤相比，在每例患者的整体DTC中，推定的干/祖细胞的平均患病率为72%，中位患病率为65%（范围，33-100%），而在原发性肿瘤中报告了这种表型。
Purpose: The presence of disseminated tumor cells (DTC) in the bone marrow of breast cancer patients is an acknowledged independent prognostic factor. The biological metastatic potential of these cells has not yet been shown. The presence of putative breast cancer stem cells is shown both in primary tumors and distant metastases. These cells with a CD44(+)CD24(-/low) phenotype represent a minor population in primary breast cancer and are associated with self-renewal and tumorigenic potential. Recognizing the potential effect of prevalence of putative stem cells among DTC, we evaluated the bone marrow DTC.Experimental Design: We employed the double/triple-staining immunohistochemistry protocol and modified the established bone marrow cytokeratin (CK) staining protocol by adding steps for additional antigens, CD44 and/or CD24. We evaluated 50 bone marrow specimens, previously categorized as CK+ from early breast cancer patients. CK+ cells were examined for CD44 and CD24 expression by light microscopy, fluorescence microscopy, and spectral imaging. Results: We detected the putative stem cell - like phenotype in all CK+ specimens. The mean prevalence of putative stem/progenitor cells was 72% and median prevalence was 65% (range, 33-100%) among the overall DTC per patient, compared with primary tumors where this phenotype is reported in