Relevance of Ki-67 antigen expression and K-ras mutation in colorectal liver metastases.
OBJECTIVE
The liver is a frequent site of metastases from colorectal cancer. While these lesions are potentially amenable to surgical resection, they are usually very aggressive, and recurrence is frequent. Mutations of the proto-oncogene K- ras are thought to impart a strong growth signal to tumour cells and are closely associated with the development of malignancies of the colon and rectum. Hepatic metastases from colorectal cancer have notably elevated proliferative rates. The present study was performed to investigate the relationship between proliferation or K- ras mutation and prognosis following curative resection of colorectal liver metastases.


METHODS
Colorectal liver metastases from 41 patients undergoing curative hepatic resection were examined for proliferation status and presence of K- ras mutations. The proliferative activity was assessed by Ki-67 immunohistochemistry. DNA from the same tissue samples was screened for point mutations in codon 12 of the K- ras gene using a novel microplate-based allelic-specific hybridization assay. Ki-67 scores and K- ras status were then related with patient survival as determined through retrospective analysis.


RESULTS
Median survival was 40 months. Patients with high Ki-67 scores (> or = 50%) had significantly shorter median survival compared with those with low scores (30 vs 44 months, log-rank P=0.02). A high Ki-67 score was an independent negative prognostic factor by multivariate regression analysis (relative risk=3.04, P=0.036). K- ras point mutations were detected in 6/41 patients (15%), but mutational status did not correlate with Ki-67 score or survival.


CONCLUSIONS
These findings suggest that the tumour proliferative index is a useful predictor of aggressive tumour behaviour and an indicator of patient survival. The presence of K- ras mutations does not appear to correlate with tumour proliferation status or patient survival.
Department of General and Vascular Surgery, Johann Wolfgang Goethe-University, 60590 Frankfurt am Main, Germany.
H
H
Petrowsky
I
I
Sturm
O
O
Graubitz
D A
DA
Kooby
E
E
Staib-Sebler
C
C
Gog
C H
CH
Köhne
T
T
Hillebrand
P T
PT
Daniel
Y
Y
Fong
M
M
Lorenz
D000328:Adult; D000368:Aged; D002455:Cell Division; D015179:Colorectal Neoplasms / Q000473:pathology*; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis*; D008113:Liver Neoplasms / Q000235:genetics / Q000276:immunology / Q000401:mortality* / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D017354:Point Mutation; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D015996:Survival Rate
D019394:Ki-67 Antigen; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas