Detection of tumor cell dissemination in pancreatic ductal carcinoma patients by CK 20 RT-PCR indicates poor survival.
OBJECTIVE
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.
Soeth
Edlyn
E
Section Molecular Oncology, Department for General Surgery and Thoracic Surgery, University Clinic Schleswig-Holstein, Campus Kiel, Germany.
Grigoleit
Urte
U
Moellmann
Barbara
B
Röder
Christian
C
Schniewind
Bodo
B
Kremer
Bernd
B
Kalthoff
Holger
H
Vogel
Ilka
I
D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D019046:Bone Marrow Neoplasms / Q000556:secondary; D021441:Carcinoma, Pancreatic Ductal / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D007381:Intermediate Filament Proteins / Q000378:metabolism*; D053554:Keratin-20; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating; D010190:Pancreatic Neoplasms / Q000401:mortality* / Q000473:pathology*; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
D014408:Biomarkers, Tumor; D007381:Intermediate Filament Proteins; C507499:KRT20 protein, human; D053554:Keratin-20