PMID- 25679065
OWN - NLM
STAT- MEDLINE
DCOM- 20151117
LR  - 20161125
IS  - 1533-4058 (Electronic)
IS  - 1533-4058 (Linking)
VI  - 23
IP  - 2
DP  - 2015 Feb
TI  - Detection of MDM2/CDK4 amplification in lipomatous soft tissue tumors from 
      formalin-fixed, paraffin-embedded tissue: comparison of multiplex 
      ligation-dependent probe amplification (MLPA) and fluorescence in situ 
      hybridization (FISH).
PG  - 126-33
LID - 10.1097/PDM.0000000000000041 [doi]
AB  - In this study, the detection of MDM2 and CDK4 amplification was evaluated in 
      lipomatous soft tissue tumors using multiplex ligation-dependent probe 
      amplification (MLPA), a PCR-based technique, in comparison with fluorescence in 
      situ hybridization (FISH). These 2 techniques were evaluated in a series of 77 
      formalin-fixed, paraffin-embedded lipomatous tumors (27 benign adipose tumors, 28 
      atypical lipomatous tumors/well-differentiated liposarcomas, 18 dedifferentiated 
      liposarcomas, and 4 pleomorphic liposarcomas). Using MLPA, with a cut-off ratio 
      of >2, 36/71 samples (22 atypical lipomatous tumors/well-differentiated 
      liposarcomas, and 14 dedifferentiated liposarcomas) showed MDM2 and CDK4 
      amplification. Using FISH as gold standard, MLPA showed a sensitivity of 90% 
      (36/40) and a specificity of 100% (31/31) in detecting amplification of MDM2 and 
      CDK4 in lipomatous soft tissue tumors. In case of high-level amplification 
      (MDM2-CDK4/CEP12 ratio >5), concordance was 100%. Four cases of atypical 
      lipomatous tumor/well-differentiated liposarcoma (4/26, 15%) with a low MDM2 and 
      CDK4 amplification level (MDM2-CDK4/CEP12 ratio ranging between 2 and 2.5) 
      detected by FISH showed no amplification by MLPA, although gain of MDM2 and CDK4 
      (ratios ranging between 1.6 and 1.9) was seen with MLPA. No amplification was 
      detected in benign lipomatous tumors and pleomorphic liposarcomas. Furthermore, 
      there was a very high concordance between the ratios obtained by FISH and MLPA. 
      In conclusion, MLPA proves to be an appropriate and straightforward technique for 
      screening MDM2/CDK4 amplification in lipomatous tumors, especially when a correct 
      cut-off value and reference samples are chosen, and could be considered a good 
      alternative to FISH to determine MDM2 and CDK4 amplification in liposarcomas. 
      Moreover, because MLPA, as a multiplex technique, allows simultaneous detection 
      of multiple chromosomal changes of interest, it could be in the future a very 
      reliable and fast molecular analysis on paraffin-embedded material to test for 
      other diagnostically, prognostically, or therapeutically relevant genomic 
      mutations in lipomatous tumors.
FAU - Creytens, David
AU  - Creytens D
AD  - *Department of Pathology, Ghent University and Ghent University Hospital, Ghent, 
      Belgium daggerDepartment of Pathology, Diakonessenhuis Utrecht, Utrecht double daggerDepartment of 
      Pathology, GROW-School for Oncology and Developmental Biology, Maastricht 
      University Medical Center, Maastricht, The Netherlands.
FAU - van Gorp, Joost
AU  - van Gorp J
FAU - Ferdinande, Liesbeth
AU  - Ferdinande L
FAU - Speel, Ernst-Jan
AU  - Speel EJ
FAU - Libbrecht, Louis
AU  - Libbrecht L
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Appl Immunohistochem Mol Morphol
JT  - Applied immunohistochemistry & molecular morphology : AIMM
JID - 100888796
RN  - 1HG84L3525 (Formaldehyde)
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)
SB  - IM
MH  - Adipose Tissue/*metabolism
MH  - Cyclin-Dependent Kinase 4/genetics/*metabolism
MH  - Feasibility Studies
MH  - Formaldehyde
MH  - Gene Amplification
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/methods
MH  - Lipoma/*diagnosis/pathology
MH  - Liposarcoma/*diagnosis/pathology
MH  - Multiplex Polymerase Chain Reaction/methods
MH  - Paraffin Embedding
MH  - Proto-Oncogene Proteins c-mdm2/genetics/*metabolism
MH  - Reproducibility of Results
MH  - Soft Tissue Neoplasms/*diagnosis/pathology
MH  - Tissue Fixation
EDAT- 2015/02/14 06:00
MHDA- 2015/11/18 06:00
CRDT- 2015/02/14 06:00
PHST- 2015/02/14 06:00 [entrez]
PHST- 2015/02/14 06:00 [pubmed]
PHST- 2015/11/18 06:00 [medline]
AID - 00129039-201502000-00007 [pii]
AID - 10.1097/PDM.0000000000000041 [doi]
PST - ppublish
SO  - Appl Immunohistochem Mol Morphol. 2015 Feb;23(2):126-33. doi: 
      10.1097/PDM.0000000000000041.