Abstract
BackgroundUterine adenosarcoma (UA) is an extremely rare sarcoma subtype. There has been limited evaluation of the immune microenvironment in these tumors. The objective of this study is to examine and describe the immune infiltrate and PD-1/PD-L1 expression in UA and to correlate these changes in the tumor micro-environment with the overall survival status or the disease-free survival status (DFSS), respectively.MethodsPatients (pts) treated at our center from 1982 to 2014 with UA were identified. Fifteen cases had tumor paraffin-embedded blocks available. Immunohistochemistry studies for CD3, CD8, FOXP3, CD163, PD-1 and PD-L1 (clone 22C3) were performed. Image analysis was used to assess the density (cells/mm2), except in PD-L1, where the percentage of membranous staining on tumor cells was noted.ResultsImmune infiltrate analysis median (range) density in cells/mm2 varied broadly: CD3 178 (15–802); CD8 117 (11–661); FoxP3 4.8 (0.2–82); CD163 791 (264–1861); and PD1 5 (1–65). 3 cases had rare (1%) PD-L1 tumor membranous labeling. The reports yielded that ten pts were alive, and 5 were dead. Pts who were alive had significant higher CD3 and CD8 median densities in tumors than those who were dead (p = 0.040). There was no correlation between DFSS and CD3 or CD8 median densities. Patients who had no local recurrence had significantly higher CD3 and CD8 median densities in tumors than those who had local recurrence (p = 0.040).ConclusionsIn conclusion, this is the first report characterizing the presence of immune infiltrate and PD-1/PD-L1 expression in UA. CD3+ CD8+ T-cells density may be prognostic. The immune-responsiveness of UA needs to be further investigated in a larger study.
Highlights
Uterine adenosarcoma (UA) is an extremely rare sarcoma subtype
Undifferentiated pleomorphic sarcoma may have the most sensitive sarcoma tumor microenvironment to immunotherapy [20]. These facts have led to the increased interest in characterizing the immune microenvironment in uterine adenosarcoma, with the hope to better understand the microenvironment of these tumors and to improve treatment and outcomes
Clinical and pathological characteristics Clinical and pathological characteristics of the 15 patients included in this study are described in Table 1, and include age, tumor size, follow-up, sarcomatous overgrowth, myometrial invasion, lymphovascular
Summary
Uterine adenosarcoma (UA) is an extremely rare sarcoma subtype. There has been limited evaluation of the immune microenvironment in these tumors. Immunotherapy trials in soft tissue and bone sarcomas, such as SARC 028, have occasionally reported responses, in one patient with uterine leiomyosarcoma. It is critically important to understand the tumor immunologic microenvironment, which may help determine which sarcomas could respond to immunotherapy. Tumor infiltrating lymphocytes (TILs) and PD-1/PD-L1 expression have been reported in soft tissue and bone sarcomas, including some uterine leiomyosarcomas and undifferentiated uterine sarcomas [12,13,14,15]. Undifferentiated pleomorphic sarcoma may have the most sensitive sarcoma tumor microenvironment to immunotherapy [20] These facts have led to the increased interest in characterizing the immune microenvironment in uterine adenosarcoma, with the hope to better understand the microenvironment of these tumors and to improve treatment and outcomes
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