PMID- 9713346
OWN - NLM
STAT- MEDLINE
DCOM- 19980915
LR  - 20220321
IS  - 0022-3417 (Print)
IS  - 0022-3417 (Linking)
VI  - 185
IP  - 2
DP  - 1998 Jun
TI  - Molecular abnormalities in liposarcoma: role of MDM2 and CDK4-containing 
      amplicons at 12q13-22.
PG  - 188-90
AB  - It has recently been shown that mdm2 overexpression with stabilization of p53 
      represents a characteristic of retroperitoneal 
      well-differentiated-dedifferentiated, here renamed evolved (WD-E), liposarcomas 
      at the immunocytochemical, molecular, and cytogenetic level. This make-up appears 
      to be confined to half the cases in non-retroperitoneal well-differentiated 
      liposarcomas. Since in different tumours MDM2 amplification involves amplicons 
      encompassing flanking genes, such as CDK4, the possibility was investigated that 
      in these tumours, CDK4 could act as an alternative or additional gene involved in 
      the transformation mechanism. Forty-one retroperitoneal (R)/non-retroperitoneal 
      (NR) well-differentiated-dedifferentiated (WD-DD) and 33 myxoid/round cell 
      liposarcomas were reanalysed by immunocytochemical, molecular (nine cases) and 
      fluorescence in situ hybridization (FISH) (one case) techniques. The results 
      showed that all but one R WD-E cases carried the mdm2+, p53+, cdk4+ 
      immunophenotype. In NR-WD liposarcomas, this immunophenotype was shared in five 
      cases and the remainder showed mdm2+, p53-, cdk4+ in four and mdm2-, p53-, cdk4+ 
      in one case, showing ring chromosomes by FISH analysis. TP53 mutations are 
      confirmed to be closely correlated with NR-DD liposarcomas and no CDK4 
      involvement was found in the myxoid/round cell liposarcoma group. As well as 
      confirming the synergistic effect of MDM2 and CDK4, these results are consistent 
      with the concept that amplicon(s) excluding MDM2 may contribute to transformation 
      and support a role of CDK4 in opposing p53 function, particularly in NR WD 
      liposarcoma.
FAU - Pilotti, S
AU  - Pilotti S
AD  - Division of Anatomic Pathology and Cytopathology, Istituto Nazionale per lo 
      Studio e la Cura dei Tumori, Milano, Italy.
FAU - Della Torre, G
AU  - Della Torre G
FAU - Lavarino, C
AU  - Lavarino C
FAU - Sozzi, G
AU  - Sozzi G
FAU - Minoletti, F
AU  - Minoletti F
FAU - Vergani, B
AU  - Vergani B
FAU - Azzarelli, A
AU  - Azzarelli A
FAU - Rilke, F
AU  - Rilke F
FAU - Pierotti, M A
AU  - Pierotti MA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Pathol
JT  - The Journal of pathology
JID - 0204634
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 2.3.2.27 (MDM2 protein, human)
RN  - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2)
RN  - EC 2.7.11.22 (CDK4 protein, human)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 4)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
SB  - IM
MH  - Blotting, Southern
MH  - *Chromosomes, Human, Pair 12
MH  - Cyclin-Dependent Kinase 4
MH  - Cyclin-Dependent Kinases/*genetics
MH  - *Gene Amplification
MH  - Gene Expression Regulation
MH  - Genes, p53
MH  - Humans
MH  - Immunohistochemistry
MH  - Immunophenotyping
MH  - In Situ Hybridization, Fluorescence
MH  - Liposarcoma/*genetics
MH  - *Nuclear Proteins
MH  - Proto-Oncogene Proteins/*genetics
MH  - Proto-Oncogene Proteins c-mdm2
EDAT- 1998/08/26 02:23
MHDA- 2000/06/20 09:00
CRDT- 1998/08/26 02:23
PHST- 1998/08/26 02:23 [pubmed]
PHST- 2000/06/20 09:00 [medline]
PHST- 1998/08/26 02:23 [entrez]
AID - 10.1002/(SICI)1096-9896(199806)185:2<188::AID-PATH53>3.0.CO;2-2 [pii]
AID - 10.1002/(SICI)1096-9896(199806)185:2<188::AID-PATH53>3.0.CO;2-2 [doi]
PST - ppublish
SO  - J Pathol. 1998 Jun;185(2):188-90. doi: 
      10.1002/(SICI)1096-9896(199806)185:2<188::AID-PATH53>3.0.CO;2-2.