The CD44+/CD24-phenotype relates to 'triple-negative' state and unfavorable prognosis in breast cancer patients
The CD44+/CD24-phenotype relates to 'triple-negative' state and unfavorable prognosis in breast cancer patients
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DOI：
10.1007/s12032-010-9530-3
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发表时间：
2011-09-01
期刊：
影响因子：
3.4
通讯作者：
Koukourakis, Michael I.
中科院分区：
文献类型：
--
作者：
Giatromanolaki, Alexandra;Sivridis, Efthimios;Koukourakis, Michael I.
据报道，乳腺癌含有CD44+/CD24-肿瘤细胞亚群，具有干细胞样特性。本研究探讨这两种分子在肿瘤侵袭和预后中的意义。使用与干细胞样属性(CD44、CD24)、“三态”(ER、PR、c-erb-B2)和血管生成(CD31)相关的标记，在石蜡切片上研究了139例乳腺癌的表型特征。有10%的CD44和CD24癌细胞的肿瘤被认为是阳性的。CD44+和CD24+乳腺癌的患病率分别为51.8%和41.7%。CD44(+)/CD24(-)表型的患者在发病时的中位年龄较低10岁，并且肿瘤呈三阴性状态。他们经历了一个不利的预后。CD44表达缺失与淋巴结转移有关，与CD24状态无关，而CD44和CD24表达缺失与组织学分级高和预后不良有关，值得注意的是在所有表型中，CD44和CD24表达缺失与预后不良有关。在多因素分析中，CD44(-)/CD24(-)表型、淋巴结转移、血管密度和ER-/PR-/c-erbB-2比值是独立的预后变量。结论：对CD44/CD24状态的评估可以揭示乳腺癌患者不同的临床行为亚群。三阴性肿瘤对当前化疗的不良反应及其与CD44(+)/CD24(-)表型的密切联系，使CD44成为乳腺癌患者有吸引力的治疗选择。CD44(-)/CD24(-)表型与预后的相关性有待进一步研究。
Breast carcinomas have been reported to contain a subpopulation of CD44+/CD24- tumor cells with stem cell-like properties. This study investigates the significance of these two molecules in connection with tumor aggression and prognosis. The phenotypic profile of 139 breast carcinomas was investigated in paraffin sections using markers previously associated with stem cell-like properties (CD44, CD24), the "triple-state" (ER, PR, c-erb-B2), and angiogenesis (CD31). Tumors with > 10% of CD44 and CD24 cancer cells were considered positive. The prevalence of CD44+ and CD24+ breast carcinomas in the series was 51.8% and 41.7%, respectively. Patients with the CD44(+)/CD24(-) phenotype had a 10-year lower median age at presentation and harbored tumors with a triple-negative state. They experienced an unfavorable prognosis. Lack of CD44 expression was associated with lymph node involvement, regardless of CD24 status, whereas the lack of both CD44 and CD24 was connected with high histologic grade and unfavorable prognosis which, notably, was the worse among all phenotypes. In multivariate analysis, the CD44(-)/CD24(-) phenotype, the nodal involvement, the vascular density and the ER-/PR-/c-erbB-2-profile were independent prognostic variables. It is concluded that assessment of the CD44/CD24 status may reveal distinct subgroups of breast cancer patients with different clinical behavior. The unsatisfactory response of the triple-negative tumors to current chemotherapy and their intimate link with the CD44(+)/CD24(-) phenotype, makes CD44 targeting an attractive therapeutic alternative for breast cancer patients. The strong association between the CD44(-)/CD24(-) phenotype and prognosis requires further investigation.