What tumor marker is used for sarcoma diagnosis?

Sarcoma Tumor Markers for Diagnosis

There is no single universal tumor marker for sarcoma diagnosis; instead, molecular genetic testing for characteristic genetic aberrations is the gold standard ancillary technique for diagnosing specific sarcoma subtypes. 1

Diagnostic Approach for Sarcomas

Sarcoma diagnosis relies on a multi-step process:

• Morphologic diagnosis based on microscopic examination of histologic sections remains the gold standard 1
• Ancillary techniques support morphologic diagnosis, including:
  • Immunohistochemistry 1
  • Classical cytogenetics 1
  • Molecular genetic testing 1

Molecular Genetic Testing in Sarcoma Diagnosis

Molecular genetic testing has emerged as a particularly powerful ancillary approach because:

• Many sarcoma types harbor characteristic genetic aberrations 1
• These include single base-pair substitutions, deletions, amplifications, and translocations 1
• Most molecular testing uses fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR)-based methods 1

Specific Genetic Markers by Sarcoma Type

Malignant Round Cell Tumors

• Ewing's sarcoma: t(11;22)(q24;q12) resulting in EWS-FLI1 fusion 1
• Desmoplastic small round cell tumor: t(11;22)(p13;q12) resulting in EWS-WT1 fusion 1
• Alveolar rhabdomyosarcoma: t(2;13)(q35;q14) resulting in PAX3-FKHR fusion 1

Lipomatous Tumors

• Myxoid/round cell liposarcoma: t(12;16)(q13;p11) resulting in TLS-CHOP fusion 1
• Atypical lipomatous tumor/well-differentiated liposarcoma: Amplification of region 12q14-15, including MDM2, CDK4, HMGA2, SAS, GL1 1

Other Sarcomas

• Synovial sarcoma: t(X;18)(p11;q11) resulting in SYT-SSX1 or SYT-SSX2 fusion 1
• Clear cell sarcoma: t(12;22)(q13;q12) resulting in EWS-ATF1 fusion 1
• Dermatofibrosarcoma protuberans: t(17;22)(q22;q13) resulting in COL1A1-PDGFB fusion 1

Emerging Biomarkers

• Cell-surface vimentin (CSV) has been proposed as a potential universal marker for detecting circulating tumor cells from different types of sarcomas 2
• NTRK gene fusions have been identified in certain sarcomas, particularly infantile fibrosarcoma (>90% have ETV6-NTRK3 fusion) 1
• Specific immunohistochemical markers can serve as surrogates for molecular genetic alterations:
  • STAT6 for solitary fibrous tumor 3
  • H3K27me3 for malignant peripheral nerve sheath tumor 3
  • MDM2 for dedifferentiated liposarcoma 3

Important Clinical Considerations

• Molecular genetic analysis involves complex test methods that are not absolutely sensitive or specific 1
• Test results must always be interpreted in the context of clinical and pathologic features 1
• Testing should be performed by a pathologist with expertise in sarcoma diagnosis and molecular diagnostic techniques 1
• Unlike carcinomas, traditional serum tumor markers (like CEA, CA-125, etc.) are not routinely used for sarcoma diagnosis 1, 4

Diagnostic Pitfalls to Avoid

• Relying on a single test result can lead to misdiagnosis due to nonspecificity issues 4
• Some sarcomas can express epithelial markers and be misclassified as carcinomas 1
• Keratin positivity in epithelioid sarcomas or small round blue cell sarcomas can lead to erroneous classification 1
• Limited biopsies may not capture characteristic histologic features necessary for accurate diagnosis 3