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

Abstract

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.

Fig. 1

Detection rate of disseminated tumor cells in blood and bone marrow of patients with pancreatic carcinoma in dependence on the UICC-classification. Results of UICC-stages I and II are combined and presented by the white columns, while stage III and stage IV are shown in hatched and black, respectively. The first set of three columns refers to all analyzed bone marrow samples (n=135), the second set to all analyzed blood samples (n=154) and the third to all patients analyzed (n=172)

Fig. 2

Overall survival rate of patients (n=159) with pancreatic ductal carcinoma in dependence on the tumor differentiation. The patients with well- and moderately-differentiated tumors (grade 1 and grade 2; n=117; thin line) are compared with patients with poorly differentiated tumors (grade 3; n=42; bold line). The difference in survival with an advantage for patients with a grade 1 or grade 2 tumor compared to a grade 3 tumor was statistically significant (P=0.045)

Fig. 3

Overall survival rate of patients (n=172) with pancreatic ductal carcinoma in dependence on the detection of disseminated tumor cells in the bone marrow and/or the blood. CK 20-negative patients (n=91; thin line) were compared to CK 20-positive individuals (n=81; bold line). The difference in survival showing an advantage for the negatively tested patients was statistically significant (P=0.05)

Fig. 4

Overall survival rate of pancreatic ductal carcinoma patients (n=117) with well- or moderately-differentiated (grade 1 or grade 2) tumors in dependence on the detection of disseminated tumor cells in the bone marrow and/or the blood. CK 20-negative results (n=64; thin line) were compared with CK 20-positive results (n=53; bold line). The difference in survival with an advantage for the negatively tested patients was statistically significant (P=0.046)