Jauch K W, Heiss M M, Gruetzner U, Funke I, Pantel K, Babic R, Eissner H J, Riethmueller G, Schildberg F W
Department of Surgery, Ludwig-Maximilians University, Munich, Germany.
J Clin Oncol. 1996 Jun;14(6):1810-7. doi: 10.1200/JCO.1996.14.6.1810.
Monoclonal antibodies (mabs) against components of the cytoskeleton such as cytokeratins allow single disseminated epithelial carcinoma cells to be detected in the bone marrow. The aim of this study was to examine the prognostic relevance of these cells in patients with gastric cancer and to evaluate by multivariate analysis their predictive value compared with conventional risk factors.
A total of 1 x 10(6) cells from bone marrow aspirates were screened immunoctochemically for the presence and absolute number of disseminated tumor cells using mab CK2 to cytokeratin component no. 18. Patients were monitored prospectively for 30.6 +/- 15.2 months.
Between one and 122 CK2-positive cells per 1 million mononuclear bone marrow cells were present in 95 of 180 patients (53%). A similar prevalence of 51% was found in curatively operated patients (55 of 109). Comparison with conventional prognostic risk factors showed a correlation of cell dissemination with pathohistologic tumor (pT) stage (P = .07) and Bormann classification (P = .022). Tumor-cell content in the bone marrow predicted disease-free and overall survival in curatively resected patients (P = .007 and P = .049, respectively). Multivariate analysis, which included established risk factors, showed that extent of tumor-cell dissemination was an independent prognostic parameter for disease-free survival in T1/2 tumors (P = .014; relative risk [RR], 1.84; 95% confidence interval [CI], 1.35 to 2.52), in intestinal type carcinomas according to Laurén (P = .008; RR, 1.62; 95% CI, 1.23 to 2.12), and in patients without lymph node involvement (P = .004; RR, 2.43; 95% CI, 1.22 to 4.82).
Presence of disseminated tumor cells in bone marrow is indicative of systemic disease even in early-stage gastric cancer. The extent of tumor-cell presence in bone marrow correlates with prognosis in curatively resected patients. Therefore, a positive bone marrow finding may be a selection criteria for adjuvant treatment because of minimal residual tumor load.
针对细胞骨架成分（如细胞角蛋白）的单克隆抗体可使骨髓中单个播散的上皮癌细胞得以检测。本研究旨在探讨这些细胞在胃癌患者中的预后相关性，并通过多因素分析评估其与传统危险因素相比的预测价值。
使用针对细胞角蛋白成分18的单克隆抗体CK2，对1×10⁶份骨髓抽吸物中的细胞进行免疫组织化学筛查，以检测播散肿瘤细胞的存在及绝对数量。对患者进行前瞻性监测30.6±15.2个月。
180例患者中有95例（53%）每百万单核骨髓细胞中存在1至122个CK2阳性细胞。在根治性手术患者中也发现了类似的51%的患病率（109例中的55例）。与传统预后危险因素比较显示，细胞播散与病理组织学肿瘤（pT）分期（P = 0.07）和博尔曼分类（P = 0.022）相关。骨髓中的肿瘤细胞含量可预测根治性切除患者的无病生存期和总生存期（分别为P = 0.007和P = 0.049）。多因素分析纳入既定危险因素后显示，肿瘤细胞播散程度是T1/2期肿瘤无病生存期的独立预后参数（P = 0.014；相对危险度[RR]，1.84；95%可信区间[CI]，1.35至2.52），在劳伦分类的肠型癌中（P = 0.008；RR，1.62；95%CI，1.23至2.12），以及在无淋巴结受累的患者中（P = 0.004；RR，2.43；95%CI，1.22至4.82）。
即使在早期胃癌中，骨髓中存在播散肿瘤细胞也提示存在全身性疾病。骨髓中肿瘤细胞的存在程度与根治性切除患者的预后相关。因此，骨髓检查结果阳性可能因残留肿瘤负荷最小而成为辅助治疗的选择标准。
