Detection of tumor cell dissemination in pancreatic ductal carcinoma patients by CK 20 RT-PCR indicates poor survival

Purpose: 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. Methods: 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. Results: 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). Conclusions: 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.