Cure Alveolar Soft Part Sarcoma International (iCureASPS)

Expression of lymphocyte immunoregulatory biomarkers in bone and soft-tissue sarcomas


Abstract

Despite advances in our understanding of the underlying molecular drivers of sarcomas, few treatments are available with proven benefit for advanced metastatic sarcomas. Immunotherapy has value in this setting for some types of cancers, but sarcomas, with their multiplicity of rare types, have not been characterized in detail for their expression of targetable immune biomarkers. This study provides the most systematic evaluation to date of tumor-infiltrating lymphocytes and immune checkpoint biomarker expression in sarcomas. We examined by morphology and immunohistochemistry 1072 sarcoma specimens representing 22 types, in addition to 236 benign bone and soft-tissue tumors. Genomically-complex sarcoma types-those driven by mutations and/or copy-number alterations-had much higher numbers of tumor-infiltrating lymphocytes than translocation-associated sarcomas. Prior exposure to radiotherapy was associated with increased immune infiltrates. Higher lymphocytic infiltration was associated with better overall survival among the non-translocation-associated sarcomas. Expression of PD-1 and CD56 were associated with worse overall survival. LAG-3 and TIM-3, two emerging immune checkpoints, were frequently expressed in most sarcoma types. Indeed, most cases positive for PD-(L)1 coexpressed one or both of these novel biomarkers, providing a potential rationale in support for trials targeting LAG-3 and/or TIM-3 in conjunction with PD-1 inhibition.

https://pubmed.ncbi.nlm.nih.gov/31263176/

DNA copy number changes in alveolar soft part sarcoma: a comparative genomic hybridization study
S Kiuru-Kuhlefelt et al. Mod Pathol. 1998 Mar.


https://pubmed.ncbi.nlm.nih.gov/9521467/

Materials and methods
Patient tumor samples
Formalin-fixed, paraffin-embedded tissue microarrays were constructed at The University of British Columbia (Vancouver, BC, Canada) and at Mount Sinai Hospital (New York, NY, USA). From The University of British Columbia, 14 tissue microarrays were included: TMA-01-003 (synovial sarcoma and differential diagnoses, 82 cases in duplicate) [40]; TMA-03-008 (chondroid tumors, 121 cases in duplicate) [41]; TMA-06-001A (gastrointestinal stromal tumors, 148 cases in duplicate) [42]; TMA-06-007 (myxoid liposarcomas, 69 cases in triplicate) [43]; TMA-09-006 (epithelioid sarcoma and differential diagnoses, 53 cases in duplicate) [44]; TMA-10-004 (28 chordomas, in duplicate); TMA-10-009 (8 alveolar soft part sarcomas, 2 alveolar rhabdomyosarcomas, and 2 desmoplastic small round cell tumors, in triplicate) [44]; TMA-12-004 (BCL2-positive tumors, 35 cases in triplicate) [45]; TMA-12-005 (pediatric spindle cell lesions, 134 cases in duplicate) [45]; TMA-12-006 (translocation-associated sarcomas, 10 cases in duplicate) [45]; TMA-12-010 (5 dedifferentiated liposarcomas and 5 undifferentiated pleomorphic sarcomas, in duplicate) [45]; TMA-14-006 (4 myxoid liposarcomas, 3 myxofibrosarcomas, 3 chondrosarcomas, 1 synovial sarcoma, and 1 malignant peripheral nerve sheath tumor, in duplicate) [46]; TMA-14-007 (dedifferentiated liposarcomas with well-differentiated areas, both components for 57 cases in duplicate) [47]; and TMA-MPNST (malignant peripheral nerve sheath tumor and differential diagnoses, 176 cases in duplicate) [48]. From the Mount Sinai Hospital, three tissue microarrays were included: MSH-OSa (osteosarcomas, 280 cases in duplicate); MSH-SS (synovial sarcomas, 70 cases in duplicate); and MSH-UPS (75 undifferentiated pleomorphic sarcomas, 52 myxofibrosarcomas, 18 leiomyosarcomas, 13 dedifferentiated liposarcomas, 10 dermatofibrosarcoma protuberans, and differential diagnoses; 210 cases total in duplicate).