Limited role of TP53 and TP53-related genes in myxoid liposarcoma.
OBJECTIVE
Circumstantial evidence suggests that genetic changes may lead to tumor progression within the myxoid liposarcoma tumors (MLTs) carrying non-random chromosomal translocation t(12;16).


METHODS
To address this subject an immunophenotypic analysis, applying antibodies against proteins encoded by TP53, MDM2 and CDK4 genes, complemented by molecular analysis of eight suitable cases, was performed on 104 consecutive cases. Chromosomal translocations were assessed either by cytogenetic analysis or by RT-PCR in 9 suitable cases and chimeric transcripts were found in all cases but two pleomorphic liposarcomas.


RESULTS
Based on immunophenotyping and tumor site, the case material consisted of three groups. The first one was made up of 92 non-retroperitoneal cases carrying a null p53, mdm2, cdk4 immunophenotype, which remained unchanged over the time of recurrences and along the gamut of histologic subtypes. The second group was represented by five p53+, mdm2-, cdk4- non-retroperitoneal cases, 4 of which were further analysed by PCR-SSCP for p53 mutation. The immunophenotypic profile of these cases, complemented by the molecular findings, supported a role of TP53 in tumor progression in three high-grade MLTs. The third group, consisting of 7 retroperitoneal cases, showed a heterogeneous immunophenotype, sharing immunophenotypic and molecular features with the well-differentiated/evoluted (dedifferentiated) liposarcoma group.


CONCLUSIONS
TP53 mutations seem to play a role in tumor progression in a few cases of MLTs (2.8%) showing more aggressive histologic characteristics. The unexpected finding that a number of retroperitoneal LMTs display the immunophenotypic profile of the well differentiated/evoluted (dedifferentiated) liposarcomas, deserves further investigation.
Pilotti
S
S
Division of Anatomic Pathology and Cytopathology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy. pilotti@mbox.istituto-tumori.mi.it
Lavarino
C
C
Mezzelani
A
A
Della Torre
C
C
Minoletti
F
F
Sozzi
G
G
Azzarelli
A
A
Rilke
F
F
Pierotti
M A
MA
D004252:DNA Mutational Analysis; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D008080:Liposarcoma / Q000235:genetics; D018208:Liposarcoma, Myxoid / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins