Chen Yanping, Song Jinlian, Jiang Yuhong, Yu Chundong, Ma Zhongliang
Department of Laboratory, Women and Children's Hospital of Qingdao Qingdao, China.
Department of Breast Surgery, The Affiliated Hospital of Qingdao University Qingdao, China.
Int J Clin Exp Pathol. 2015 Sep 1;8(9):11287-95. eCollection 2015.
Cells with unique phenotypes and stem cell-like properties have been found to exist in breast cancer. The aim of the present study was to study the relationship of CD24, CD44, CD44(+)/CD24(-/low) and CD44(-)/CD24(+) tumor phenotypes' with clinico-pathological features, chemotherapy response and with prognosis.
The study included paraffin-embedded tissues of 140 primary and secondary invasive ductal carcinoma samples. All the patients received routine chemotherapy. Expression of CD24, CD44, ER, PR, and Her2 were assayed immunohistochemically. We applied double-staining immunohistochemistry for the detection of CD44(+)/CD24(-/low), CD44(+)/CD24 (+), CD44(-)/CD24(-) and CD44(-)/CD24(+) cells. The association between the proportions of CD44(+)/CD24(-/low) and CD44(-)/CD24(+) and clinicopathological features, chemotherapy response and with prognosis of these patients was evaluated.
CD24 expression was not significantly associated with tumor characteristics, but was significantly associated with poor prognostic variables including ER-, PR-, HER2(+) and triple negative (TN) phenotype; There was no association of CD44 with nodal status, age or HER2 expression. In the correlation analysis, CD24 expression was positively associated with chemotherapy response (P = 0.018), however, CD44 expression was not associated with pathological response to chemotherapy When both markers are considered, the CD44(+)/CD24(-) phenotype had the poor prognosis. The proportion of CD44+/CD24- tumor cells was significantly associated with lymph node involvement, recurrent or metastatic tumors and ER/PR status. High CD44(+)/CD24(-) phenotype had poor response to chemotherapy. The median disease-free survival (DFS) of patients with and without CD44(+)/CD24(-/low) tumor cells were 19.8 ± 2.6 months and 31.7 ± 4.2 months, and the median overall survival (OS) of patients with and without CD44(+)/CD24(-/low) tumor cells were 33.5 ± 2.8 months and 51.4 ± 3.9 months, respectively, and with both univariate and multivariate analyses showing that the proportion of CD44(+)/CD24(-/low) tumor cells was strongly correlated with DFS and OS. However, the CD44(-)/CD24(+), CD44(+)/CD24(+), CD44(-)/CD24 (-) phenotype had no relation with prognosis.
There was significant correlation between CD44(+)/CD24(-/low) tumor cell prevalence and tumor metastasis, prognosis and chemotherapy response. The CD44(+)/CD24(-) phenotype may be an important factor for malignant relapse following surgical resection and chemotherapy in patients with invasive ductal carcinoma.
已发现在乳腺癌中存在具有独特表型和干细胞样特性的细胞。本研究的目的是探讨CD24、CD44、CD44(+)/CD24(-/低)和CD44(-)/CD24(+)肿瘤表型与临床病理特征、化疗反应及预后的关系。
本研究纳入140例原发性和继发性浸润性导管癌样本的石蜡包埋组织。所有患者均接受常规化疗。采用免疫组织化学方法检测CD24、CD44、雌激素受体（ER）、孕激素受体（PR）和人表皮生长因子受体2（Her2）的表达。我们应用双重免疫组织化学染色检测CD44(+)/CD24(-/低)、CD44(+)/CD24(+)、CD44(-)/CD24(-)和CD44(-)/CD24(+)细胞。评估CD44(+)/CD24(-/低)和CD44(-)/CD24(+)细胞比例与这些患者的临床病理特征、化疗反应及预后的相关性。
CD24表达与肿瘤特征无显著相关性，但与包括ER阴性、PR阴性、HER2阳性和三阴性（TN）表型等不良预后变量显著相关；CD44与淋巴结状态、年龄或HER2表达无关。在相关性分析中，CD24表达与化疗反应呈正相关（P = 0.018），然而，CD44表达与化疗的病理反应无关。当同时考虑这两个标志物时，CD44(+)/CD24(-)表型预后较差。CD44+/CD24-肿瘤细胞比例与淋巴结受累、复发或转移肿瘤以及ER/PR状态显著相关。高CD44(+)/CD24(-)表型对化疗反应较差。有和无CD44(+)/CD24(-/低)肿瘤细胞患者的无病生存期（DFS）中位数分别为19.8±2.6个月和31.7±4.2个月，有和无CD44(+)/CD24(-/低)肿瘤细胞患者的总生存期（OS）中位数分别为33.5±2.8个月和51.4±3.9个月，单因素和多因素分析均显示CD44(+)/CD24(-/低)肿瘤细胞比例与DFS和OS密切相关。然而，CD44(-)/CD24(+)、CD44(+)/CD24(+)、CD44(-)/CD24(-)表型与预后无关。
CD44(+)/CD24(-/低)肿瘤细胞比例与肿瘤转移、预后及化疗反应之间存在显著相关性。CD44(+)/CD24(-)表型可能是浸润性导管癌患者手术切除及化疗后恶性复发的重要因素。
