Perioperative activation of disseminated tumor cells in bone marrow of patients with prostate cancer.
Perioperative activation of disseminated tumor cells in bone marrow of patients with prostate cancer.
复制标题
前列腺癌患者骨髓中播散性肿瘤细胞的围手术期激活。
DOI：
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复制
发表时间：
2009
影响因子：
45.3
通讯作者：
C. Klein
中科院分区：
文献类型：
--
作者：
D. Weckermann;B. Polzer;Thomas Ragg;A. Blana;G. Schlimok;H. Arnholdt;S. Bertz;R. Harzmann;C. Klein
目的
前列腺癌的治疗方法有哪些？为了评估系统性疾病的动态并识别早期复发的高风险患者，我们跟踪了骨髓中播散性肿瘤细胞的命运长达10年，并对在疾病的各个阶段分离的此类细胞进行了遗传分析。
患者和方法
使用抗细胞角蛋白8、18和19的单克隆抗体A45-B/B3对384例患者的900份骨髓穿刺液进行染色。应用对数秩统计和考克斯回归分析确定术前（244例患者）和术后（214例患者）检测到的阳性细胞的预后影响。通过比较基因组杂交分析来自原发性肿瘤（n = 55）和单个播散性肿瘤细胞（n = 100）的样品。
结果
术前检测到细胞角蛋白阳性细胞是48个月内转移的最强独立危险因素（P <0.001;相对危险度[RR]，5.5; 95%CI，2.4 - 12.9）。与此相反，细胞角蛋白阳性细胞检测6个月至10年后，根治性前列腺切除术始终存在于骨髓中的患病率约为20%，但对疾病的结果没有影响。细胞角蛋白阳性细胞的特征性基因型在转移表现时被选择。
结论
前列腺癌患者骨髓中的细胞角蛋白阳性细胞只有在手术前检测到时才具有诊断相关性。因为我们不能确定显着的遗传差异术前和术后分离的肿瘤细胞转移的表现之前，我们假设存在围手术期刺激，激活播散的肿瘤细胞。因此，术前骨髓中细胞角蛋白阳性细胞的患者可能会从辅助治疗中获益。
PURPOSE
The outcome of prostate cancer is highly unpredictable. To assess the dynamics of systemic disease and to identify patients at high risk for early relapse we followed the fate of disseminated tumor cells in bone marrow for up to 10 years and genetically analyzed such cells isolated at various stages of disease.
PATIENTS AND METHODS
Nine hundred bone marrow aspirates from 384 patients were stained using the monoclonal antibody A45-B/B3 directed against cytokeratins 8, 18, and 19. Log-rank statistics and Cox regression analysis were applied to determine the prognostic impact of positive cells detected before surgery (244 patients) and postoperatively (214 patients). Samples from primary tumors (n = 55) and single disseminated tumor cells (n = 100) were analyzed by comparative genomic hybridization.
RESULTS
Detection of cytokeratin-positive cells before surgery was the strongest independent risk factor for metastasis within 48 months (P < .001; relative risk [RR], 5.5; 95% CI, 2.4 to 12.9). In contrast, cytokeratin-positive cells detected 6 months to 10 years after radical prostatectomy were consistently present in bone marrow with a prevalence of approximately 20% but had no influence on disease outcome. Characteristic genotypes of cytokeratin-positive cells were selected at manifestation of metastasis.
CONCLUSION
Cytokeratin-positive cells in the bone marrow of prostate cancer patients are only prognostically relevant when detected before surgery. Because we could not identify significant genetic differences between pre- and postoperatively isolated tumor cells before manifestation of metastasis, we postulate the existence of perioperative stimuli that activate disseminated tumor cells. Patients with cytokeratin-positive cells in bone marrow before surgery may therefore benefit from adjuvant therapies.
DOI：
10.1097/s0022-5347(01)68600-2
发表时间：
2005-10
期刊：
The Journal of urology
影响因子：
--
作者：
P. Walsh
通讯作者：
P. Walsh
影响因子：
11.2
作者：
Holcomb, Ilona N.;Grove, Douglas I.;Kinnunen, Martin;Friedman, Cynthia L.;Gallaher, Ian S.;Morgan, Todd M.;Sather, Cassandra L.;Delrow, Jeffrey J.;Nelson, Peter S.;Lange, Paul H.;Ellis, William J.;True, Lawrence D.;Young, Janet M.;Hsu, Li;Trask, Barbara J.;Vessella, Robert L.
通讯作者：
Vessella, Robert L.