Davidson Ben, Dong Hiep Phuc, Holth Arild, Berner Aasmund, Risberg Björn
Pathology Clinic, Rikshospitalet Medical Center, Montebello, Oslo, Norway.
Breast J. 2008 Sep-Oct;14(5):476-82. doi: 10.1111/j.1524-4741.2008.00625.x. Epub 2008 Jul 24.
This objective of this study was to investigate the expression of chemokine receptors in tumor cells and leukocytes in breast carcinoma effusions. The expression of leukocyte markers (CD3/4/8/14/16/19) and chemokine receptors (CXCR1/4, CCR2/5/7) was studied in 21 breast carcinoma effusions using flow cytometry. Breast carcinoma cells expressed CXCR4 in 7/21 (33%) effusions, with less frequent expression of CXCR1, CCR5, and CCR7. CXCR2 and CCR2 were absent. Lymphocytes showed frequent CXCR4, CCR5, and CCR7 expression, while CXCR1, CXCR2, CCR2 were rarely or never detected. Macrophages expressed all six receptors except for CXCR2. Comparative analysis of breast carcinoma effusions with previously studied ovarian and cervical/endometrial adenocarcinomas (ACs) showed significantly higher CXCR4 expression in breast carcinoma cells compared to the other gynecological ACs (p = 0.001). Breast and cervical/endometrial carcinoma effusions showed different expression of chemokine receptors in lymphocytes (lower CXCR1, higher CXCR4 and CCR7 levels; p = 0.012, p = 0.005, p < 0.001, respectively) and macrophages (higher CCR7 levels; p < 0.001), as well as lower CD8 counts (p < 0.001) and higher CD19 counts (p = 0.001) compared to ovarian carcinoma effusions. Higher numbers of CD8-positive lymphocytes (p = 0.080) and higher CCR7 monocyte expression (p = 0.087) were associated with a trend for shorter disease-free survival. In conclusion, breast carcinoma cells express CXCR4, a unique feature among metastatic ACs in effusions, with rare expression of other chemokine receptors. Chemokine receptor expression in leukocytes and lymphocyte counts significantly differ from those of ovarian carcinoma effusions. The prognostic role of CCR7 expression in monocytes and CD8 counts in breast carcinoma effusions merits further research.
本研究的目的是调查趋化因子受体在乳腺癌积液中的肿瘤细胞和白细胞中的表达情况。使用流式细胞术研究了21例乳腺癌积液中白细胞标志物（CD3/4/8/14/16/19）和趋化因子受体（CXCR1/4、CCR2/5/7）的表达。乳腺癌细胞在7/21（33%）的积液中表达CXCR4，CXCR1、CCR5和CCR7的表达频率较低。未检测到CXCR2和CCR2。淋巴细胞频繁表达CXCR4、CCR5和CCR7，而CXCR1、CXCR2、CCR2很少或从未被检测到。巨噬细胞表达除CXCR2外的所有六种受体。将乳腺癌积液与先前研究的卵巢癌和宫颈/子宫内膜腺癌（AC）进行比较分析，结果显示乳腺癌细胞中CXCR4的表达明显高于其他妇科AC（p = 0.001）。乳腺癌和宫颈/子宫内膜癌积液在淋巴细胞（CXCR1较低、CXCR4和CCR7水平较高；p分别为0.012、0.005、p < 0.001）和巨噬细胞（CCR7水平较高；p < 0.001）中的趋化因子受体表达不同，与卵巢癌积液相比，CD8计数较低（p < 0.001）且CD19计数较高（p = 0.001）。较高数量的CD8阳性淋巴细胞（p = 0.080）和较高的CCR7单核细胞表达（p = 0.087）与无病生存期缩短的趋势相关。总之，乳腺癌细胞表达CXCR4，这是积液中转移性AC的一个独特特征，其他趋化因子受体表达罕见。白细胞中的趋化因子受体表达和淋巴细胞计数与卵巢癌积液有显著差异。CCR7在乳腺癌积液单核细胞中的表达和CD8计数的预后作用值得进一步研究。
