Abstract We assessed the frequency of programmed death-ligand 1 (PD-L1) expression by immunohistochemistry (IHC) in a cohort of 522 sarcomas from 457 patients, incuding a subset of 46 patients with 63 matched samples from local recurrence or metastases with primary tumours and/or metachronous metastases. We also investigated the correlation of PD-L1 with the presence and degree of tumour-infiltrating lymphocytes (TILs) in a subset of cases. IHC was performed using the PD-L1 SP263 companion kit (VENTANA) on tissue microarrays from an archival cohort. Evaluation of PD-L1 and TILs was performed on full sections for a subset of 23 cases. Fisher’s exact and Mann Whitney test were used to establish significance (P <0.05). PD-L1 positive expression (≥1%) was identified in 31% of undifferentiated pleomorphic sarcomas, 29% of angiosarcomas, 26% of rhabdomyosarcomas, 18% of myxofibrosarcomas, 11% of leiomyosarcomas and 10% of dedifferentiated liposarcomas. Negative expression was present in all atypical lipomatous tumous/well-differentiated lipoasarcomas, myxoid liposarcomas, synovial sarcomas, pleomorphic liposarcomas, and Ewing sarcomas. PD-L1 IHC was concordant in 81% (38 of 47) of matched/paired samples. PD-L1 IHC was discordant in 19% (9 of 47 matched/paired samples), displaying differences in the proportion of cells expressing PD-L1 amongst paired samples with the percentage of PD-L1-positive cells increasing in the metastatic/recurrent site compared to the primary in 6 of 9 cases (67%). Significant correlation between PD-L1 expression and the degree of TILs was exclusively identified in the general cohort of leiomyosarcomas, but not in other sarcoma subtypes or in metastatic/recurrent samples. We conclude that the prevalence of PD-L1 expression in selected sarcomas is variable and likely to be clone dependent. Importantly, we demonstrated that PD-L1 can objectively increase in a small proportion of metastases/recurrent sarcomas, offering the potential of treatment benefit to immune checkpoint inhibitors in this metastatic setting.
Abstract We report a case of a 51-year-old man with primary diagnosis of Ewing sarcoma confined to the soft tissue, associated with EWSR1-FLI1 gene fusion demonstrated by fluorescence in situ hybridization (FISH). Six years after the diagnosis, immunohistochemistry for NTRK (neurotrophic receptor tyrosine kinase 1–3) was performed on this tumor using 2 Pan-Trk rabbit monoclonal antibodies, A7H6R (Cell Signaling Technology, Danvers, Mass) and EPR17341 (Abcam, Cambridge, Mass). Both clones showed diffuse moderate to strong cytoplasmic expression including presence of nuclear stain. RNA sequencing demonstrated the co-occurrence of MTMR2-NTRK2 , a novel gene fusion, in the same tumor block used for EWSR1 FISH testing. While FISH for NRK2 did not confirm gene rearrangement, an atypical signal pattern was identified. This case challenges the concept that NTRK fusions are mutually exclusive with other oncogenic drivers. The clinical course of this patient has also been unusual as the tumor has followed an indolent course with no evidence of recurrent or metastatic disease.
The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Data sharing not applicable to this article as no datasets were generated or analysed during the current study
Aims Synovial sarcoma is defined by recurrent t(X;18)(p11;q11) translocations creating SS18 – SSX1 , SS18 – SSX2 or SS18 – SSX4 fusions. Recently, a novel rabbit monoclonal antibody designed to identify these fusions (SS18–SSX, clone E9X9V) was proposed to be highly specific (100%), but not completely sensitive (95%) for this diagnosis. Another antibody designed to identify the C‐terminal end of SSX (SSX_CT, clone E5A2C) was proposed to be highly sensitive (100%), but not completely specific (96%). We sought to validate these antibodies in an independent cohort. Methods and results We performed immunohistochemistry for SS18–SSX and SSX_CT on 39 synovial sarcoma samples from 25 patients with confirmed gene rearrangements. Thirty‐four (87%) and 36 (92%) were positive for SS18–SSX and SSX_CT, respectively. False‐negative staining was associated with suboptimally handled small biopsies and decalcified specimens, even when staining was diffuse and strong in subsequent optimally processed excisions and non‐decalcified areas. None of 580 non‐synovial sarcoma tumours (76 whole sections, 504 TMA samples) were positive for SS18–SSX (100% specificity), whereas 39 (93% specificity) were positive for SSX_CT. Conclusions SS18–SSX fusion‐specific IHC is 87–95% sensitive for the diagnosis of synovial sarcoma and highly (perhaps perfectly) specific. Therefore, positive SS18–SSX staining definitively confirms the diagnosis of synovial sarcoma. SSX_CT is less specific (93–96%) but highly sensitive (92%, but approaching 100% when suboptimally processed biopsies and decalcified specimens are excluded). Negative SSX_CT staining may therefore have an ancillary role as a rule‐out test for synovial sarcoma. We caution that both antibodies are prone to false‐negative staining in decalcified specimens.
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