[Detection of micrometastases after curative resection for ductal adenocarcinoma of the pancreas].
OBJECTIVE
Despite apparently curative resection adenocarcinomas of the pancreas early recur. Thus, the pathological examination should be enriched by sensitive methods to detect minimal residual disease (MRD). Mutant K-ras is the most promising genetic alteration in ductal adenocarcinoma and may serve to detect malignant cells by polymerase chain reaction (PCR) based techniques. Therefore, we set out to detect K-ras mutations by PCR for evaluation of MRD in patients after curative resection of pancreatic adenocarcinoma.


METHODS
Tumor tissue and corresponding paraaortic lymph nodes were obtained from 51 patients, who underwent surgery for pancreatic head tumors. The paraaortic lymph nodes were staged as tumor-free by routine histopathology in all cases diagnosed for ductal adenocarcinoma (study group, n = 40) or other tumors (control group, n = 11). Therefore, DNA of both primary tumors and lymph nodes was extracted and analysed by a PCR-based assay with respect to mutated K-ras. As a positive control the human pancreatic cancer cell line PaTu-8902 was used.


RESULTS
K-ras mutations were detected in 73 % (29/40) of primary tumors of ductal adenocarcinomas and in 17 % (5/29) in the corresponding paraaortic lymph nodes, which were diagnosed as tumor-free by routine pathology. The identical type of point mutation was found in primary tumors and corresponding lymph nodes by use of sequence specific primers. In the control group no K-ras mutation was detected.


CONCLUSIONS
Tumor cell DNA can be detected sensitively in tumor- and lymph node specimen with the described method. Routinely assessed, this method is able to detect MRD and could enrich the pathological examination, in order to determine prognostic relevant subgroups of patients.
Niedergethmann
M
M
Chirurgische Klinik, Universitätsklinikum Mannheim, Fakultät für klinische Medizin Mannheim der Universität Heidelberg, Germany.
Rexin
M
M
Knob
S
S
Hartel
M
M
Sturm
J W
JW
Richter
A
A
Post
S
S
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics* / Q000601:surgery; D001483:Base Sequence; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000032:analysis; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D008207:Lymphatic Metastasis / Q000175:diagnosis / Q000235:genetics; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000601:surgery; D010195:Pancreatitis / Q000235:genetics; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012680:Sensitivity and Specificity
D017931:DNA Primers; D004273:DNA, Neoplasm