PMID- 27684983
OWN - NLM
STAT- MEDLINE
DCOM- 20170227
LR  - 20170817
IS  - 1543-2165 (Electronic)
IS  - 0003-9985 (Linking)
VI  - 140
IP  - 10
DP  - 2016 Oct
TI  - Automated Bright-Field Dual-Color In Situ Hybridization for MDM2: Interobserver 
      Reproducibility and Correlation With Fluorescence In Situ Hybridization in a 
      Series of Soft Tissue Consults.
PG  - 1111-5
LID - 10.5858/arpa.2015-0249-OA [doi]
AB  - CONTEXT: -Atypical lipomatous tumors/well-differentiated liposarcomas contain 
      alterations in the 12q13-15 region resulting in amplification of MDM2 and nearby 
      genes. Identifying MDM2 amplification is a useful ancillary test, as the 
      histologic mimics of atypical lipomatous tumors/well-differentiated liposarcomas 
      have consistently shown a lack of MDM2 amplification. OBJECTIVE: -To assess the 
      interobserver reproducibility of a bright-field assay for MDM2 amplification 
      (dual-color, dual-hapten in situ hybridization [DDISH]) among reviewers with 
      varying degrees of experience with the assay and to assess the concordance of 
      MDM2 DDISH with MDM2 fluorescence in situ hybridization (FISH). DESIGN: -In 
      total, 102 cases were assessed in parallel for MDM2 by FISH and DDISH. MDM2 
      amplification was defined as an MDM2 to chromosome 12 ratio of 2.0 or greater, 
      whereas an MDM2 to chromosome 12 ratio of less than 2 was nonamplified. 
      Fluorescence in situ hybridization was scored in the routine clinical laboratory 
      and DDISH was evaluated by 3 different pathologists blinded to the final 
      diagnosis and FISH results. RESULTS: -Fluorescence in situ hybridization 
      categorized 27 cases (26%) as MDM2 amplified and 75 cases (74%) as nonamplified; 
      the consensus DDISH diagnosis was 98% concordant with FISH. Agreement between 
      MDM2 DDISH by each reviewer and MDM2 FISH was highly concordant (99%, 98%, and 
      98%, respectively, for reviewers 1, 2 and 3). The kappa agreement of the 3 reviewers 
      scoring DDISH was excellent (kappa = 0.949, 0.95, and 0.95, respectively, for 
      reviewers 1, 2, and 3). CONCLUSIONS: -This study highlights excellent concordance 
      between DDISH and FISH in MDM2 copy number assessment. Moreover, excellent 
      interobserver reproducibility of the DDISH assay was found among reviewers with 
      varying levels of experience evaluating bright-field assays.
FAU - Zhang, Gloria
AU  - Zhang G
AD  - From the Departments of Anatomic Pathology (Drs Zhang and Goldblum) and Molecular 
      Pathology (Mr Lanigan and Dr Tubbs), Robert J. Tomsich Pathology and Laboratory 
      Medicine Institute, Cleveland Clinic, Cleveland, Ohio; and the Department of 
      Pathology, Huntsman Cancer Center, University of Utah, Salt Lake City (Dr 
      Downs-Kelly).
FAU - Lanigan, Christopher P
AU  - Lanigan CP
FAU - Goldblum, John R
AU  - Goldblum JR
FAU - Tubbs, Raymond R
AU  - Tubbs RR
FAU - Downs-Kelly, Erinn
AU  - Downs-Kelly E
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Arch Pathol Lab Med
JT  - Archives of pathology & laboratory medicine
JID - 7607091
RN  - EC 2.3.2.27 (MDM2 protein, human)
RN  - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2)
SB  - IM
MH  - Chromosomes, Human, Pair 12/genetics
MH  - Gene Amplification
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/*methods
MH  - Lipoma/diagnosis/*genetics
MH  - Liposarcoma/diagnosis/*genetics
MH  - *Observer Variation
MH  - Proto-Oncogene Proteins c-mdm2/*genetics
MH  - Reproducibility of Results
MH  - Sensitivity and Specificity
EDAT- 2016/09/30 06:00
MHDA- 2017/02/28 06:00
CRDT- 2016/09/30 06:00
PHST- 2016/09/30 06:00 [entrez]
PHST- 2016/09/30 06:00 [pubmed]
PHST- 2017/02/28 06:00 [medline]
AID - 10.5858/arpa.2015-0249-OA [doi]
PST - ppublish
SO  - Arch Pathol Lab Med. 2016 Oct;140(10):1111-5. doi: 10.5858/arpa.2015-0249-OA.