Review Article

Microsatellite Instability in Sarcoma: Fact or Fiction?

Table 1

Chronological summary of MSI assessment in sarcomas.

AuthorsYearSarcoma populationTissue sourceMethod of microsatellite assessmentBethesda consensus panelFrequency of MSIClinical correlation

Wooster et al. [42]1994Soft-tissue sarcomas
( 𝑛 = 1 8 )
Unspecified tumor preparation; peripheral blood (genomic control DNA)PCR; 6% agarose electrophoresis, subcloning, and sequence analysis0/5 markers assessed11% (2/18) MSI at one lociNot assessed
Belchis et al. [37]1996Osteosarcoma
( 𝑛 = 1 8 )
FFPE tumor specimens; unspecified normal tissuePCR; gel electrophoresis; autoradiography0/5 markers assessed44% (8/18) with MSI at β‰₯1 loci (2/8 were MSI-H)Not assessed
Tarkkanen et al. [43]1996Bone sarcomas
( 𝑛 = 2 9 )
Unspecified tumor preparation; peripheral blood (genomic control DNA)PCR; gel electrophoresis; autoradiography0/5 markers assessedNo MSI observedn/a
Martin et al. [38]1998Bone and soft tissue
( 𝑛 = 1 6 )
Fresh frozen tumor and peripheral blood (genomic control DNA)PCR; gel electrophoresis; autoradiography0/5 markers assessed44% (7/16) with MSI at β‰₯1 loci (3/7 MSI-H)MSI associated with poor clinical outcome
Aue et al. [44]1998Clear cell sarcoma and melanoma
( 𝑛 = 1 1 )
FFPE specimens (tumor and genomic control DNA)PCR; gel electrophoresis; autoradiography0/5 markers assessedNo MSI observedConclude MSI analysis can be used to differentiate CCS from melanoma
Klinger et al. [39]2000Chondrosarcoma
( 𝑛 = 1 2 )
FFPE specimens (tumor and genomic control DNA)PCR; gel electrophoresis; autoradiography0/5 markers assessed50% (6/12) with MSI at β‰₯1 loci (3/6 MSI-H)Not assessed
Entz-Werle et al. [45]2003Osteosarcoma
( 𝑛 = 5 4 )
Fresh frozen tumor and peripheral blood (genomic control DNA)Fluorescence-based PCR; automated sequencing1/5 markers assessedNo MSI instability observedn/a
Ohali et al. [40]2004Ewing sarcoma
( 𝑛 = 2 3 )
Fresh frozen tumor and peripheral blood (genomic control DNA)PCR; gel electrophoresis; autoradiography2/5 markers assessed48% (11/23) with MSI at β‰₯1 loci (4/11 MSI-H)MSI associated with poor clinical outcome
RuciΕ„ska et al. [41]2005Soft-tissue sarcomas
( 𝑛 = 2 0 )
Fresh frozen tumor and peripheral blood (genomic control DNA)Fluorescence-based PCR; automated sequencing1/5 markers assessed100% (8/8) of high-grade sarcomas with MSI at β‰₯1 loci (4/8 MSI-H); No MSI in low-grade sarcomasNot assessed
Ebinger et al. [46]2005Ewing sarcoma
( 𝑛 = 1 8 )
FFPE specimens (tumor and genomic control DNA)Unspecified5/5 markers assessed6% (1/18) with MSI at one lociNot assessed
Kawaguchi et al. [56]2005STS
( 𝑛 = 4 0 )
Fresh frozen tumor and normal tissueFluorescence-based PCR; automated sequencing1/5 markers assessed25% (10/40) with MSI at β‰₯1 loci (2/10 MSI-H)Not assessed
Entz-WerlΓ© et al. [47]2005Osteosarcoma
( 𝑛 = 6 8 )** same patient cohort as [45]
Fresh frozen tumor and peripheral blood (genomic control DNA)Fluorescence-based PCR; automated sequencing1/5 markers assessedNo MSI instability observedn/a
Garcia et al. [48]2006Clear-cell sarcoma
( 𝑛 = 9 )
FFPE specimens (tumor and genomic control DNA)Fluorescence-based PCR; automated sequencing5/5 markers assessed11% (1/9) with MSI at one lociConclude MSI analysis can be used to differentiate CCS from melanoma
Alldinger et al. [49]2007Ewing sarcoma
( 𝑛 = 5 5 )
FFPE tumor specimens and peripheral blood (genomic control DNA)Fluorescence-based PCR; automated sequencing5/5 markers assessed14% (8/55) with MSI at one lociMSI not predictive of clinical outcome

MSI: microsatellite instability; STS: soft-tissue sarcoma; FFPE: formalin-fixed, paraffin-embedded; PCR: polymerase chain reaction; CCS: clear-cell sarcoma.