Cyclooxygenase-2 expression in primary breast cancers predicts dissemination of cancer cells to the bone marrow.
Cyclooxygenase-2 expression in primary breast cancers predicts dissemination of cancer cells to the bone marrow.
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DOI：
10.1007/s10549-008-0135-x
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发表时间：
2009-09
影响因子：
3.8
通讯作者：
Cristofanilli M
中科院分区：
文献类型：
--
作者：
Lucci A;Krishnamurthy S;Singh B;Bedrosian I;Meric-Bernstam F;Reuben J;Broglio K;Mosalpuria K;Lodhi A;Vincent L;Cristofanilli M
环氧合酶-2（COX 2）在乳腺癌从癌前表型到临床转移的各个阶段的进展中起作用。乳腺癌通常转移到骨，临床前研究表明COX 2参与了这一过程。在手术时检测到患者骨髓中播散的肿瘤细胞与随后临床骨转移的发展相关。因此，为了研究COX 2是否对人类乳腺癌转移很重要，我们通过免疫染色分析了112例可手术I、II或III期患者原发肿瘤的COX 2蛋白表达，并确定其与骨髓微转移（BMM）的相关性。我们用单克隆抗体免疫染色检测原发性肿瘤中的COX 2蛋白，用上皮细胞角蛋白免疫染色和形态学标准检测骨髓中的肿瘤细胞。COX 2在原发性乳腺癌中的表达与BMM以高度统计学显著的方式相关（P = 0.006）。我们对原发肿瘤中COX 2阳性与其他临床相关指标的相关性进行了统计分析，结果显示COX 2阳性与高核分级相关（P = 0.0004）。此外，我们能够检测COX 2蛋白在BMM的免疫染色。这些研究表明，原代乳腺癌细胞中产生的COX 2可能对BMM的初始发展至关重要，BMM随后可能导致乳腺癌患者的溶骨性骨转移，COX 2抑制剂可能有助于阻止这一过程。
Cyclooxygenase-2 (COX2) plays a role in breast cancer progression at various stages starting from pre-malignant phenotype to clinical metastasis. Breast cancer metastasizes commonly to the bone and preclinical studies suggest an involvement of COX2 in this process. Detection of disseminated tumor cells in the bone marrow of patients at the time of surgery correlates with the subsequent development of clinical bone metastasis. Therefore, to investigate whether COX2 is important for breast cancer metastasis in humans, we analyzed COX2 protein expression by immunostaining of primary tumors from 112 operable stages I, II, or III patients and determined its correlation with bone marrow micrometastasis (BMM). We detected COX2 protein in primary tumors by immunostaining with a monoclonal antibody, and tumor cells present in the bone marrow by immunostaining for epithelial cytokeratins and by morphological criteria. COX2 expression in primary breast cancer correlated with BMM in a highly statistically significant manner (P = 0.006). Our statistical analyses of correlations of the COX2 positivity in primary tumor with other clinically relevant indicators revealed that COX2 positivity correlates with high nuclear grade (P = 0.0004). Furthermore, we were able to detect COX2 protein in BMM by immunostaining. These studies indicate that COX2 produced in primary breast cancer cells may be vital to the initial development of BMM that may subsequently lead to osteolytic bone metastases in patients with breast cancer, and that COX2 inhibitors may be useful in halting this process.
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