Genetic detection of lymph node micrometastases: a selection criterion for liver transplantation in patients with liver metastases after colorectal cancer.
BACKGROUND
Liver transplantation for nonresectable liver metastases from colorectal cancer was abandoned in 1994 on account of high recurrence rates. The aim of this study was to investigate whether the genetic detection of micrometastases in histologically negative lymph nodes of the primary colon cancer could be applied to select patients for liver transplantation.


METHODS
We analyzed 21 patients with colorectal cancer who had undergone liver transplantation between 1983 and 1994 for liver metastases. Eleven patients were histologically lymph node negative at the time of surgery; ten patients with lymph node metastases served as control group. DNA sequencing was used to screen tumor material for p53 and K-ras mutations. Mutant allele-specific amplification (MASA) was then used to search for micrometastases in DNA from regional lymph nodes of the primary colorectal cancer.


RESULTS
p53 and K-ras mutations were detected in 12 (57%) and 3 (14%) of 21 patients in the colorectal cancer, respectively. The mutations were confirmed in the corresponding liver metastases. Of 11 patients with histologically negative lymph nodes, nine were eligible for MASA due to presence of p53 or K-ras mutation. MASA revealed six of nine patients to be genetically positive for micrometastases. Three patients were both genetically and histologically negative. These three patients showed a significantly longer overall survival (P = 0.011) of 4, 5, and 20 years, respectively.


CONCLUSIONS
We conclude that the genetic detection of micrometastases by MASA could be a powerful prognostic indicator for selecting patients with colorectal liver metastases who could benefit from liver transplantation.
Kappel
Sonja
S
Department of Surgical Research, Medical University of Vienna, Vienna, Austria.
Kandioler
Daniela
D
Steininger
Rudolf
R
Längle
Friedrich
F
Wrba
Friedrich
F
Ploder
Martin
M
Berlakovich
Gabriela
G
Soliman
Thomas
T
Hetz
Hubert
H
Rockenschaub
Susanne
S
Roth
Erich
E
Mühlbacher
Ferdinand
F
D000328:Adult; D001483:Base Sequence; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000556:secondary* / Q000601:surgery*; D016031:Liver Transplantation; D008207:Lymphatic Metastasis / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D016159:Tumor Suppressor Protein p53; D016283:Proto-Oncogene Proteins p21(ras)