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The utility of fluorescence in situ hybridization (FISH) in the diagnosis of myxoid soft tissue neoplasms

Downs-Kelly, Erinn; Goldblum, John R.; Patel, Rai M.; Weiss, Sharon W.; Folpe, Andrew L.; Mertens, Fredrik LU ; Hartke, Marybeth; Tubbs, Rayinond R. and Skacel, Marek (2008) In American Journal of Surgical Pathology 32(1). p.8-13
Abstract
Diagnosing myxoid soft tissue neoplasms can be challenging because of overlapping histologic features. Distinct chromosomal translocations have been identified in several myxoid sarcomas, including t(12;16)(q13;p11) FUS-DDIT3 in myxoid liposarcoma, t(7,-16)(q34;p11) FUS-CREB3L2 in low-grade fibromyxoid sarcoma, and t(9;22)(q31;q12) EWSRINR4A3 in extraskeletal myxoid chondrosarcoma. These recurrent chromosomal alterations are attractive targets for diagnostic studies. To that end, dual-color, break-apart fluorescence in situ hybridization (FISH) probes spanning the genomic regions of EWSRI (22q12), DDIT3 (12q13), and FUS (16p11) (Vysis, Downer's Grove, IL) were evaluated in formalin-fixed, paraffin-embedded tissues from myxoid neoplasms,... (More)
Diagnosing myxoid soft tissue neoplasms can be challenging because of overlapping histologic features. Distinct chromosomal translocations have been identified in several myxoid sarcomas, including t(12;16)(q13;p11) FUS-DDIT3 in myxoid liposarcoma, t(7,-16)(q34;p11) FUS-CREB3L2 in low-grade fibromyxoid sarcoma, and t(9;22)(q31;q12) EWSRINR4A3 in extraskeletal myxoid chondrosarcoma. These recurrent chromosomal alterations are attractive targets for diagnostic studies. To that end, dual-color, break-apart fluorescence in situ hybridization (FISH) probes spanning the genomic regions of EWSRI (22q12), DDIT3 (12q13), and FUS (16p11) (Vysis, Downer's Grove, IL) were evaluated in formalin-fixed, paraffin-embedded tissues from myxoid neoplasms, including intramuscular myxoma (it 10), myxoid liposarcoma (n = 18) low-grade fibromyxoid sarcoma (n = 10), extraskeletal myxoid chondrosarcoma (n = 13), and myxofibrosarcoma (n = 8). Of the myxoid liposarcomas, 18/18 cases had a rearrangement of the DDIT3 gene, with 17/18 (94.4%) showing both DDIT3 and FUS gene rearrangements. A FUS gene rearrangement was identified in 7/10 (70%) of lowgrade fibromyxoid sarcomas, with no changes involving EWSRI or DDIT3. An EWSRI translocation was seen in 6/13 (46.2%) of extraskeletal myxoid chondrosarcomas, without changes in DDIT3 or FUS genes. The remaining neoplasms studied showed no rearrangements involving DDIT3, FUS, or EWSRI genes. In conclusion, interphase FISH using DDIT3 and FUS probes identifies the characteristic translocation in myxoid liposarcoma. FUS and EWSRI probes are useful in confirming the diagnosis of low-grade fibromyxoid sarcoma and extraskeletal myxoid chondrosarcoma, respectively. The specificity of the probes is documented as none of the non-translocation-associated myxoid tumors showed genomic abnormalities with the probes tested. FISH is capable of providing specific ancillary information useful in this often difficult differential diagnosis. (Less)
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author
organization
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Contribution to journal
publication status
published
subject
keywords
extraskeletal myxoid chondrosarcoma, fibromyxoid sarcoma, low-grade, fluorescence in situ hybridization, myxoid liposarcoma
in
American Journal of Surgical Pathology
volume
32
issue
1
pages
8 - 13
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000252135300002
  • scopus:37549059599
ISSN
1532-0979
language
English
LU publication?
yes
id
338d5a83-78b2-4e2c-bc95-7109dc83427a (old id 1200122)
date added to LUP
2008-09-12 11:10:50
date last changed
2017-09-10 03:51:10
@article{338d5a83-78b2-4e2c-bc95-7109dc83427a,
  abstract     = {Diagnosing myxoid soft tissue neoplasms can be challenging because of overlapping histologic features. Distinct chromosomal translocations have been identified in several myxoid sarcomas, including t(12;16)(q13;p11) FUS-DDIT3 in myxoid liposarcoma, t(7,-16)(q34;p11) FUS-CREB3L2 in low-grade fibromyxoid sarcoma, and t(9;22)(q31;q12) EWSRINR4A3 in extraskeletal myxoid chondrosarcoma. These recurrent chromosomal alterations are attractive targets for diagnostic studies. To that end, dual-color, break-apart fluorescence in situ hybridization (FISH) probes spanning the genomic regions of EWSRI (22q12), DDIT3 (12q13), and FUS (16p11) (Vysis, Downer's Grove, IL) were evaluated in formalin-fixed, paraffin-embedded tissues from myxoid neoplasms, including intramuscular myxoma (it 10), myxoid liposarcoma (n = 18) low-grade fibromyxoid sarcoma (n = 10), extraskeletal myxoid chondrosarcoma (n = 13), and myxofibrosarcoma (n = 8). Of the myxoid liposarcomas, 18/18 cases had a rearrangement of the DDIT3 gene, with 17/18 (94.4%) showing both DDIT3 and FUS gene rearrangements. A FUS gene rearrangement was identified in 7/10 (70%) of lowgrade fibromyxoid sarcomas, with no changes involving EWSRI or DDIT3. An EWSRI translocation was seen in 6/13 (46.2%) of extraskeletal myxoid chondrosarcomas, without changes in DDIT3 or FUS genes. The remaining neoplasms studied showed no rearrangements involving DDIT3, FUS, or EWSRI genes. In conclusion, interphase FISH using DDIT3 and FUS probes identifies the characteristic translocation in myxoid liposarcoma. FUS and EWSRI probes are useful in confirming the diagnosis of low-grade fibromyxoid sarcoma and extraskeletal myxoid chondrosarcoma, respectively. The specificity of the probes is documented as none of the non-translocation-associated myxoid tumors showed genomic abnormalities with the probes tested. FISH is capable of providing specific ancillary information useful in this often difficult differential diagnosis.},
  author       = {Downs-Kelly, Erinn and Goldblum, John R. and Patel, Rai M. and Weiss, Sharon W. and Folpe, Andrew L. and Mertens, Fredrik and Hartke, Marybeth and Tubbs, Rayinond R. and Skacel, Marek},
  issn         = {1532-0979},
  keyword      = {extraskeletal myxoid chondrosarcoma,fibromyxoid sarcoma,low-grade,fluorescence in situ hybridization,myxoid liposarcoma},
  language     = {eng},
  number       = {1},
  pages        = {8--13},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {American Journal of Surgical Pathology},
  title        = {The utility of fluorescence in situ hybridization (FISH) in the diagnosis of myxoid soft tissue neoplasms},
  volume       = {32},
  year         = {2008},
}