PMID- 17895748 OWN - NLM STAT- MEDLINE DCOM- 20071101 LR - 20220316 IS - 0147-5185 (Print) IS - 0147-5185 (Linking) VI - 31 IP - 10 DP - 2007 Oct TI - Detection of MDM2-CDK4 amplification by fluorescence in situ hybridization in 200 paraffin-embedded tumor samples: utility in diagnosing adipocytic lesions and comparison with immunohistochemistry and real-time PCR. PG - 1476-89 AB - Atypical lipomatous tumor/well-differentiated liposarcomas and dedifferentiated liposarcomas are characterized by the amplification of MDM2 and CDK4 genes. To evaluate the accuracy of fluorescence in situ hybridization (FISH) analysis in the differential diagnosis of adipose tissue tumors, we investigated MDM2-CDK4 status by FISH, real-time polymerase chain reaction (PCR) [quantitative PCR (Q-PCR)] and immunohistochemistry (IHC) in a series of 200 adipose tumors. First, we evaluated MDM2-CDK4 amplification and expression in a series of 94 well-defined adipose tissue tumors. Results showed that FISH was interpretable in 45 of 50 cases (90%), and was more specific and sensitive than Q-PCR and IHC. We then used the same techniques as complementary diagnostic tools in a series of 106 adipose and soft tissue tumors of unclear diagnosis to distinguish between (i) lipomas and atypical lipomatous tumor/well-differentiated liposarcomas, (ii) malignant undifferentiated tumors and dedifferentiated liposarcomas, and (iii) a variety of benign tumors and liposarcomas. Our results indicate that although helpful, IHC alone is often insufficient to solve diagnostic problems. FISH and Q-PCR methods gave concordant results and were equally informative in most cases. However, the proportion of noninterpretable cases was slightly higher with FISH than with Q-PCR. When tumor cells represented a minor component of the tumor tissue, such as with inflammatory tumors, FISH was more powerful than Q-PCR by allowing visualization of individual cells. In conclusion, we recommend that the evaluation of MDM2-CDK4 amplification using FISH or Q-PCR be used to supplement IHC analysis when diagnosis of adipose tissue tumors is not possible based on clinical and histologic information alone. FAU - Sirvent, Nicolas AU - Sirvent N AD - Laboratoire de Genetique Somatique des Tumeurs Solides, Faculte de Medecine, CNRS UMR 6543, Nice University Hospital, avenue de Valombrose, 06100 Nice, France. FAU - Coindre, Jean-Michel AU - Coindre JM FAU - Maire, Georges AU - Maire G FAU - Hostein, Isabelle AU - Hostein I FAU - Keslair, Frederique AU - Keslair F FAU - Guillou, Louis AU - Guillou L FAU - Ranchere-Vince, Dominique AU - Ranchere-Vince D FAU - Terrier, Philippe AU - Terrier P FAU - Pedeutour, Florence AU - Pedeutour F LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Surg Pathol JT - The American journal of surgical pathology JID - 7707904 RN - 0 (Biomarkers, Tumor) 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 - Adipocytes/metabolism/pathology MH - Adipose Tissue/metabolism/pathology MH - Adolescent MH - Adult MH - Aged MH - Biomarkers, Tumor/genetics/metabolism MH - Cyclin-Dependent Kinase 4/*genetics/metabolism MH - Female MH - Gene Expression Profiling/methods MH - Humans MH - Immunohistochemistry/*methods MH - In Situ Hybridization, Fluorescence/*methods MH - Lipoma/*genetics/metabolism MH - Liposarcoma/*diagnosis/genetics/metabolism MH - Male MH - Middle Aged MH - *Nucleic Acid Amplification Techniques MH - Paraffin Embedding MH - Proto-Oncogene Proteins c-mdm2/*genetics/metabolism MH - Reproducibility of Results MH - Reverse Transcriptase Polymerase Chain Reaction MH - Soft Tissue Neoplasms/*diagnosis/genetics/metabolism EDAT- 2007/09/27 09:00 MHDA- 2007/11/02 09:00 CRDT- 2007/09/27 09:00 PHST- 2007/09/27 09:00 [pubmed] PHST- 2007/11/02 09:00 [medline] PHST- 2007/09/27 09:00 [entrez] AID - 00000478-200710000-00003 [pii] AID - 10.1097/PAS.0b013e3180581fff [doi] PST - ppublish SO - Am J Surg Pathol. 2007 Oct;31(10):1476-89. doi: 10.1097/PAS.0b013e3180581fff.