Prognostic significance of proliferative activity, DNA-ploidy, p53 and Ki-ras point mutations in colorectal liver metastases.
Paired colorectal liver metastases (CLM) and normal tissue samples from a consecutive series of 36 patients were studied prospectively. MIB-1 expression was studied by immunohistochemistry on paraffin-embedded sections. DNA ploidy and S-phase fraction (SPF) measurements were performed by flow cytometry on frozen tissues. Mutations within the p53 (exons 5-8) and c-Ki-ras (codons 12 and 13) genes were detected by PCR single-strand conformation polymorphism analysis followed by sequencing. A high correlation was observed between the MIB-1 LI and SPF value (rho=0.81; P<0.01). Moreover, p53 gene mutations were associated with either high MIB-1 LI and high SPF. In univariate analysis, SPF and MIB-1 levels were related to risk of death. The association between overall survival and DNA-ploidy or p53 mutations did not reach statistical significance, but a slightly better survival was observed for patients either with DNA-diploid tumours or without mutations (P=0.05 and P=0.06, respectively). SPF was shown by multivariate Cox model analysis to be an independent prognostic variable and thus it might be a useful prognostic factor in patients with CLM.
Russo
A
A
Department of Clinical Oncology Research, University of Palermo, Italy.
Migliavacca
M
M
Bazan
V
V
Maturi
N
N
Morello
V
V
Dardanoni
G
G
Modica
G
G
Bazan
P
P
Albanese
I
I
La Farina
M
M
Tomasino
R M
RM
D000328:Adult; D000368:Aged; D034961:Antigens, Nuclear; D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D016158:Genes, p53 / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen; D008113:Liver Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009687:Nuclear Proteins / Q000032:analysis / Q000276:immunology; D011003:Ploidies; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D011446:Prospective Studies; D016196:S Phase; D015996:Survival Rate
D034961:Antigens, Nuclear; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D009687:Nuclear Proteins