[Frequency, distribution and prognostic relevance of p53 mutations in soft tissue sarcomas].
Soft tissue sarcomas although rarely occurring (about 1% of malignant tumors), are because of their histo-morphological diversity and often similar appearance to tumor-like lesions difficult to characterize and estimate in their tumor biological behaviour. Analysis of molecular characteristics as alterations in tumor-suppressor and oncogenes may allow insight in STS genesis. We have chosen the in carcinomas well, but in STS not comprehensively investigated tumor-suppressor gene p53 for mutational analysis. In 16 out of 146 STS patients we could identify p53-mutations. In a multivariate Cox-regression analysis prognosis was correlated with the p53-mutation type. However, only patients with non-frameshift mutations possessed a poorer prognosis (RR = 2.42; p = 0.014) in comparison to patients without mutations, but frameshift-mutations didn't seem to affect prognosis negatively. Compiling our results and those of the literature an overall frequency of 16.3% of p53-mutations in STS, with various frequencies in different entities is detectable. STS specific hotspots are not recognizable. Rather mutational hotspots in codons 175, 245, 248 and 273 well known from studies in carcinomas are also apparent in STS. Summarizing, we want to state that the occurrence of p53-mutations (non-frameshift mutations) is of prognostic importance in STS. Combination of histo-pathological, clinical and molecular characteristics may allow to distinguish in future different groups of patients for an individual treatment.
Taubert
H
H
Institut für Pathologie, Martin-Luther-Universität Halle-Wittenberg.
Würl
P
P
Meye
A
A
Bache
M
M
Kroll
J
J
Lautenschläger
C
C
Thamm
B
B
Holzhausen
H J
HJ
Hinze
R
R
Schmidt
H
H
Berger
D
D
Rath
F W
FW
D003062:Codon; D016368:Frameshift Mutation; D016158:Genes, p53; D006801:Humans; D015999:Multivariate Analysis; D009154:Mutation; D017354:Point Mutation; D011379:Prognosis; D012044:Regression Analysis; D012189:Retrospective Studies; D012509:Sarcoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D013997:Time Factors
D003062:Codon