Fehm Tanja, Krawczyk Natalia, Solomayer Erich-Franz, Becker-Pergola Graziella, Dürr-Störzer Silke, Neubauer Hans, Seeger Harald, Staebler Annette, Wallwiener Diethelm, Becker Sven
Department of Obstetrics and Gynecology, University of Tuebingen, Germany.
Breast Cancer Res. 2008;10(5):R76. doi: 10.1186/bcr2143. Epub 2008 Sep 15.
Isolated disseminated tumour cells (DTC) are regarded as surrogate markers for minimal residual disease in breast cancer. Characterisation of these cells could help understand the known limitations of adjuvant therapy. Of particular interest is their oestrogen-receptor (ER) status because endocrine adjuvant therapy remains a cornerstone of breast cancer treatment.
Bone marrow (BM) aspirates from 254 patients with primary breast cancer were included in this study. A double immunofluorescence staining procedure was established for the identification of cytokeratin (CK) positive/Eralpha-positive cells. ERalpha status of the primary tumour was assessed immunohistochemically using the same antibody against ERalpha.
In 107 of 254 (42%) breast cancer patients, CK-positive cells could be detected in the BM. More than one DTC in the BM was observed in 38 of the 107 patients. The number of detected cells ranged between 1 and 55 cells per 2 x 10(6) mononuclear cells. DTCs demonstrated ERalpha positivity in 12% of the patients. The ERalpha expression was heterogeneous in 10 of the 38 (26%) patients with more than one DTC. The concordance rate of ERalpha status between primary tumour and DTC was 28%. Only 12 of 88 patients with ERalpha-positive tumours also had ERalpha-positive DTCs.
Primary tumours and DTCs displayed a concordant ERalpha status in only 28% of cases. Most of the DTCs were ERalpha negative despite the presence of an ERalpha-positive primary tumour. These findings further underline the distinct nature of DTCs and may explain the failure rates seen in conventional endocrine adjuvant therapy.
孤立的播散肿瘤细胞（DTC）被视为乳腺癌微小残留病的替代标志物。对这些细胞的特征进行描述有助于理解辅助治疗已知的局限性。特别令人感兴趣的是它们的雌激素受体（ER）状态，因为内分泌辅助治疗仍然是乳腺癌治疗的基石。
本研究纳入了254例原发性乳腺癌患者的骨髓抽吸物。建立了双重免疫荧光染色程序以鉴定细胞角蛋白（CK）阳性/雌激素受体α（ERα）阳性细胞。使用针对ERα的相同抗体通过免疫组织化学方法评估原发性肿瘤的ERα状态。
在254例乳腺癌患者中的107例（42%）中，可在骨髓中检测到CK阳性细胞。在107例患者中的38例中观察到骨髓中有不止一个DTC。每2×10⁶个单核细胞中检测到的细胞数量在1至55个细胞之间。12%的患者中DTC表现为ERα阳性。在38例有不止一个DTC的患者中的10例（26%）中，ERα表达是异质性的。原发性肿瘤和DTC之间ERα状态的一致率为28%。在88例ERα阳性肿瘤患者中，只有12例也有ERα阳性的DTC。
原发性肿瘤和DTC仅在28%的病例中显示出一致的ERα状态。尽管原发性肿瘤为ERα阳性，但大多数DTC为ERα阴性。这些发现进一步强调了DTC的独特性质，并可能解释了传统内分泌辅助治疗中所见的失败率。
