Soeth Edlyn, Grigoleit Urte, Moellmann Barbara, Röder Christian, Schniewind Bodo, Kremer Bernd, Kalthoff Holger, Vogel Ilka
Section Molecular Oncology, Department for General Surgery and Thoracic Surgery, University Clinic Schleswig-Holstein, Campus Kiel, Germany.
J Cancer Res Clin Oncol. 2005 Oct;131(10):669-76. doi: 10.1007/s00432-005-0008-1. Epub 2005 Sep 1.
This prospective study evaluates the diagnostic potential of Cytokeratin 20 (CK 20) RT-PCR for the detection of disseminated tumor cells in bone marrow and blood of a large cohort of patients with ductal adenocarcinoma of the pancreas and the prognostic value on overall survival prediction.
Between 1994 and 2003, 172 patients (83 male, 89 female; 13-82 years) with pancreatic ductal adenocarcinoma underwent surgery. Bone marrow samples and venous blood were taken preoperatively and analyzed for disseminated tumor cells by nested CK 20 RT-PCR.
Disseminated tumor cells were detected in 81 (47.1%) of the 172 patients in the bone marrow and/or the venous blood. Overall, in 45 of the 135 (33.3%) bone marrow samples and in 52 of the 154 (33.8%) blood samples, CK 20 positive cells were detected. Detection rates increased with the UICC-tumor stage. According to Kaplan-Meier, univariate survival analysis of all 172 patients (n = 78 R0-; n = 18 R1- and n = 5 R2-resected; n = 71 palliative surgery) showed a statistically significant relationship of overall survival to radicality of the operation (P < 0.0001), the UICC-stage of the tumors (P = 0.0011) and the detection of disseminated tumor cells in bone marrow and/or venous blood (P = 0.05). Patients with well- and moderately- differentiated tumors (G1 and G2) had a significantly longer survival (P = 0.045) than patients suffering from poorly differentiated tumors (G3). A positive CK 20 status in the bone marrow and/or blood within the group of patients with G1 and G2 tumors had a significantly negative prognostic impact on their survival (P = 0.046).
Disseminated tumor cells can be detected in patients with pancreatic ductal adenocarcinoma by CK 20 RT-PCR. Detection rates are stage dependent, and survival analysis demonstrated statistically relevant data. From a clinical point of view, this finding is especially noteworthy for the group of well- and moderately-differentiated tumors.
本前瞻性研究评估细胞角蛋白20(CK 20)逆转录聚合酶链反应(RT-PCR)在检测大量胰腺导管腺癌患者骨髓和血液中播散肿瘤细胞的诊断潜力,以及对总生存预测的预后价值。
1994年至2003年期间,172例(83例男性,89例女性;年龄13 - 82岁)胰腺导管腺癌患者接受了手术。术前采集骨髓样本和静脉血,通过巢式CK 20 RT-PCR分析播散肿瘤细胞。
172例患者中,81例(47.1%)在骨髓和/或静脉血中检测到播散肿瘤细胞。总体而言,135份骨髓样本中的45份(33.3%)以及154份血液样本中的52份(33.8%)检测到CK 20阳性细胞。检测率随国际抗癌联盟(UICC)肿瘤分期增加。根据Kaplan-Meier法,对所有172例患者(n = 78例R0切除;n = 18例R1切除和n = 5例R2切除;n = 71例姑息性手术)进行单因素生存分析,结果显示总生存与手术根治性(P < 0.0001)、肿瘤UICC分期(P = 0.0011)以及骨髓和/或静脉血中播散肿瘤细胞的检测(P = 0.05)之间存在统计学显著关系。高分化和中分化肿瘤(G1和G2)患者的生存期显著长于低分化肿瘤(G3)患者(P = 0.045)。在G1和G2肿瘤患者组中,骨髓和/或血液中CK 20状态为阳性对其生存具有显著的负面预后影响(P = 0.046)。
通过CK 20 RT-PCR可在胰腺导管腺癌患者中检测到播散肿瘤细胞。检测率与分期相关,生存分析显示了具有统计学意义的数据。从临床角度来看,这一发现对于高分化和中分化肿瘤组尤为值得关注。