PMID- 27899693
OWN - NLM
STAT- MEDLINE
DCOM- 20170719
LR  - 20231213
IS  - 1940-2465 (Electronic)
IS  - 1066-8969 (Linking)
VI  - 25
IP  - 2
DP  - 2017 Apr
TI  - Performance Testing of RREB1, MYB, and CCND1 Fluorescence In Situ Hybridization 
      in Spindle-Cell and Desmoplastic Melanoma Argues for a Two-Step Test Algorithm.
PG  - 148-157
LID - 10.1177/1066896916680072 [doi]
AB  - BACKGROUND: Diagnostic confirmation of spindle-cell melanoma (SM) or desmoplastic 
      melanoma (DM) as a melanoma can be challenging. In conventional melanoma (CM), a 
      recently established fluorescence in situ hybridization (FISH) assay for RREB1, 
      MYB, CCND1 can be helpful. Here, we determined the presence of RREB1, MYB, and 
      CCND1 abnormalities in an SM/DM/mixed cohort. METHODS: We assembled 49 cases and 
      performed 3 separate hybridizations for RREB1/MYB/CCND1. We assessed clinical 
      utility in diagnostically challenging cases and performed a cost and turnaround 
      time analysis. RESULTS: With regard to the diagnosis of melanoma, the FISH assay 
      is 76% sensitive (n = 31/41 true positives melanomas) and 88% specific (n = 1/8 
      false positive desmoplastic nevi). The prevalence of abnormalities in DM is lower 
      (12/19 cases, 63%; P = .03) than in SM (15/18 cases, 83%; P = .27), mixed (4 of 4 
      cases), or the reported sensitivity in CM (345/411 cases, 84%). The implied 
      genetic differences in DM result in a higher false negative rate in DM (37%). 
      Despite these limitations, when restricted to diagnostically challenging cases (n 
      = 23), the FISH assay and, in particular, RREB1 was able to confirm melanoma in 
      70% (n = 16/23). Individual probe sensitivities ( RREB1 > MYB > CCND1) and a cost 
      and turnaround time analysis argues for a 2-step test algorithm that reduces the 
      economic impact of FISH testing considerably (~55%; n = 69 vs 123 
      hybridizations). CONCLUSION: We propose a step-by-step genetic testing algorithm 
      to support the diagnosis of melanoma in the setting of SM/DM and show that FISH 
      testing is useful in diagnostically challenging cases.
FAU - Weissinger, Stephanie E
AU  - Weissinger SE
AD  - 1 University of Ulm, Ulm, Germany.
FAU - Frick, Manfred
AU  - Frick M
AD  - 1 University of Ulm, Ulm, Germany.
FAU - Moller, Peter
AU  - Moller P
AD  - 1 University of Ulm, Ulm, Germany.
FAU - Horst, Basil A
AU  - Horst BA
AD  - 2 Columbia University Medical Center, New York, NY, USA.
FAU - Lennerz, Jochen K
AU  - Lennerz JK
AD  - 1 University of Ulm, Ulm, Germany.
AD  - 3 Massachusetts General Hospital/Harvard Medical, Boston, MA, USA.
LA  - eng
PT  - Journal Article
DEP - 20161130
PL  - United States
TA  - Int J Surg Pathol
JT  - International journal of surgical pathology
JID - 9314927
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (CCND1 protein, human)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (RREB1 protein, human)
RN  - 0 (Transcription Factors)
RN  - 136601-57-5 (Cyclin D1)
SB  - IM
MH  - Adult
MH  - Aged
MH  - *Algorithms
MH  - Biomarkers, Tumor/*analysis
MH  - Cyclin D1/analysis/genetics
MH  - DNA-Binding Proteins/analysis/genetics
MH  - Female
MH  - Gene Dosage
MH  - Genes, myb/genetics
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Melanoma/*diagnosis
MH  - Middle Aged
MH  - Sensitivity and Specificity
MH  - Skin Neoplasms/*diagnosis
MH  - Transcription Factors/analysis/genetics
MH  - Melanoma, Cutaneous Malignant
OTO - NOTNLM
OT  - BRAF
OT  - amelanotic
OT  - neurotropic
EDAT- 2016/12/03 06:00
MHDA- 2017/07/20 06:00
CRDT- 2016/12/01 06:00
PHST- 2016/12/03 06:00 [pubmed]
PHST- 2017/07/20 06:00 [medline]
PHST- 2016/12/01 06:00 [entrez]
AID - 1066896916680072 [pii]
AID - 10.1177/1066896916680072 [doi]
PST - ppublish
SO  - Int J Surg Pathol. 2017 Apr;25(2):148-157. doi: 10.1177/1066896916680072. Epub 
      2016 Nov 30.