Weihrauch Martin R, Skibowski Edmund, Koslowsky Thomas C, Voiss Wilfried, Re Daniel, Kuhn-Regnier Ferdinand, Bannwarth Carolin, Siedek Michel, Diehl Volker, Bohlen Heribert
Department of Internal Medicine I, University of Cologne, Germany.
J Clin Oncol. 2002 Nov 1;20(21):4338-43. doi: 10.1200/JCO.2002.02.152.
Micrometastatic disease in bone marrow is of prognostic significance in colorectal cancer patients. However, detection rates of standard immunocytology are relatively low. We used magnetic activated cell sorting (MACS), a highly sensitive method, to increase detection rates and correlated the presence of cytokeratin (CK)-expressing cells with clinical parameters.
Bone marrow was obtained from 51 consecutive patients with newly diagnosed colorectal adenocarcinoma who underwent primary surgery and 18 control subjects. International Union Against Cancer (UICC) stage I disease was diagnosed in 11 patients, stage II disease was diagnosed in 14 patients, stage III disease was diagnosed in 12 patients, and stage IV disease was diagnosed in 14 patients. CK-positive cells were enriched and stained with magnetically labeled CAM 5.2 antibodies directed to CK 7 and 8.
CK-positive cells were found in 33 (65%) patients and were absent in 18 (35%). Four of 11 (36%) patients with UICC stage I disease, nine of 14 (64%) with stage II diease, eight of 12 (67%) with stage III disease, and 12 of 14 (86%) with stage IV disease were CK-positive. Epithelial cells were more frequently found in pT3/4 (72%) than in pT1/2 (36%) tumors (P =.026), but there was no difference for lymph node status. CK-positive patients had a higher chance for elevated carcinoembryonic antigen (85% v 15%, P = NS) and CA 19-9 levels (92% v 8%, P =.019). There were no significant differences in CA 72-4, sex, age, tumor grading, or tumor localization regarding the presence of CK-positive cells. All control subjects were CK-negative.
In searching for micrometastases in colorectal cancer patients, we have achieved high detection rates by using MACS. The presence of these cells correlated significantly with tumor stage, tumor extension, and the tumor marker CA 19-9.
骨髓微转移疾病对结直肠癌患者具有预后意义。然而，标准免疫细胞学的检测率相对较低。我们采用磁激活细胞分选法（MACS）这一高灵敏度方法来提高检测率，并将细胞角蛋白（CK）表达细胞的存在情况与临床参数相关联。
从51例连续接受初次手术的新诊断结直肠腺癌患者及18名对照者获取骨髓。11例患者诊断为国际抗癌联盟（UICC）I期疾病，14例为II期疾病，12例为III期疾病，14例为IV期疾病。CK阳性细胞经富集并用针对CK 7和8的磁标记CAM 5.2抗体染色。
33例（65%）患者发现CK阳性细胞，18例（35%）未发现。UICC I期疾病的11例患者中有4例（36%）、II期疾病的14例患者中有9例（64%）、III期疾病的12例患者中有8例（67%）、IV期疾病的14例患者中有12例（86%）为CK阳性。上皮细胞在pT3/4肿瘤（72%）中比在pT1/2肿瘤（36%）中更常见（P = 0.026），但淋巴结状态无差异。CK阳性患者癌胚抗原升高的几率更高（85%对15%，P无统计学意义），CA 19 - 9水平也更高（92%对8%，P = 0.019）。关于CK阳性细胞的存在情况，CA 72 - 4、性别、年龄、肿瘤分级或肿瘤定位方面无显著差异。所有对照者均为CK阴性。
在寻找结直肠癌患者的微转移时，我们通过使用MACS获得了高检测率。这些细胞的存在与肿瘤分期、肿瘤浸润及肿瘤标志物CA 19 - 9显著相关。
