Schindlbeck Christian, Kampik Theresa, Janni Wolfgang, Rack Brigitte, Jeschke Udo, Krajewski Stan, Sommer Harald, Friese Klaus
1st Department of Obstetrics and Gynecology Klinikum, Ludwig-Maximilians-University, D-80337 Munich, Germany.
Breast Cancer Res. 2005;7(6):R1174-85. doi: 10.1186/bcr1360. Epub 2005 Nov 24.
The prognostic significance of disseminated tumor cells in the bone marrow (DTC-BM) of breast cancer patients has been demonstrated in many studies. Yet, it is not clear which of the primary tumors' biological factors predict hematogenous dissemination. We therefore examined 'tissue micro arrays' (TMAs) of 265 primary breast carcinomas from patients with known bone marrow (BM) status for HER2, Topoisomerase IIalpha (Top IIa), Ki 67, and p53.
BM analysis was performed by cytospin preparation and immunocytochemical staining for cytokeratin (CK). TMAs were examined by immunohistochemistry (IHC) for HER2, Top IIa, Ki 67 and p53, and fluorescence in situ hybridization (FISH) for HER2.
HER2 (2+/3+) was positive in 35/167 (21%) cases (FISH 24.3%), Top IIa (>10%) in 87/187 (46%), Ki 67 in 52/184 (28%) and p53 (>5%) in 61/174 cases (34%). Of 265 patients, 68 (25.7%) showed DTC-BM with a median of 2/2 x 106 cells (1 to 1,500). None of the examined factors significantly predicted BM positivity. Significant correlation was seen between HER2 IHC and Top IIa (p = 0.06), Ki 67 (p = 0.031), and p53 (p < .001). Top IIa correlated with Ki 67 and p53, and Ki 67 also with p53 (p = 0.004). After a median follow-up of 60.5 months (7 to 255), the presence of DTC-BM showed prognostic relevance for overall survival (p = 0.03), whereas HER2 (IHC, p = 0.04; FISH, p = 0.03) and Ki 67 (p = 0.04) correlated with disease free survival, and HER2 with distant disease free survival (IHC, p = 0.06; FISH, p = 0.05).
The congruence of the examined factors' expression rates indicates a causal line of suppressor, proliferation, and mitosis markers, and growth factor receptors. Hematogenous tumor cell spread seems to be an independent process. The examination of these factors on DTC-BM is the aim of ongoing research.
许多研究已证实乳腺癌患者骨髓中播散肿瘤细胞（DTC-BM）的预后意义。然而，尚不清楚原发性肿瘤的哪些生物学因素可预测血行播散。因此，我们检测了265例已知骨髓（BM）状态的原发性乳腺癌患者的组织微阵列（TMA），以检测HER2、拓扑异构酶IIα（Top IIa）、Ki 67和p53。
通过细胞离心涂片制备和细胞角蛋白（CK）免疫细胞化学染色进行BM分析。通过免疫组织化学（IHC）检测TMA中的HER2、Top IIa、Ki 67和p53，并通过荧光原位杂交（FISH）检测HER2。
HER2（2+/3+）在35/167例（21%）中呈阳性（FISH为24.3%），Top IIa（>10%）在87/187例（46%）中呈阳性，Ki 67在52/184例（28%）中呈阳性，p53（>5%）在61/174例（34%）中呈阳性。在265例患者中，68例（25.7%）显示DTC-BM，中位数为2/2×106个细胞（1至1500个）。所检测的因素均未显著预测BM阳性。HER2 IHC与Top IIa（p = 0.06）、Ki 67（p = 0.031）和p53（p < 0.）之间存在显著相关性。Top IIa与Ki 67和p53相关，Ki 67也与p53相关（p = 0.004）。中位随访60.5个月（7至255个月）后，DTC-BM的存在对总生存具有预后意义（p = 0.03），而HER2（IHC，p = 0.04；FISH，p = 0.03）和Ki 67（p = 0.04）与无病生存相关，HER2与远处无病生存相关（IHC，p = 0.06；FISH，p = 0.05）。
所检测因素的表达率一致性表明存在一条由抑制、增殖、有丝分裂标志物和生长因子受体组成的因果线。血行肿瘤细胞扩散似乎是一个独立的过程。对DTC-BM上这些因素的检测是正在进行的研究目标。
