Sarah Beishan Tai , Elizabeth Chun Yong Lee , Boon Yee Lim , Bavani Kannan , Jing Yi Lee , Zexi Guo , Tun Kiat Ko , Cedric Chuan-Young Ng , Bin Tean Teh , Jason Yongsheng Chan
{"title":"Tumor-Infiltrating Mast Cells in Angiosarcoma Correlate With Immuno-Oncology Pathways and Adverse Clinical Outcomes","authors":"Sarah Beishan Tai , Elizabeth Chun Yong Lee , Boon Yee Lim , Bavani Kannan , Jing Yi Lee , Zexi Guo , Tun Kiat Ko , Cedric Chuan-Young Ng , Bin Tean Teh , Jason Yongsheng Chan","doi":"10.1016/j.labinv.2024.100323","DOIUrl":null,"url":null,"abstract":"<div><p><span><span><span>Recent studies have described several molecular subtypes and deregulation of immuno-oncologic signaling pathways in </span>angiosarcoma<span>. Interestingly, mast cells were enriched in subsets of angiosarcoma, although their significance remains unknown. In this study, we aim to verify this observation using immunohistochemistry (H scores) and NanoString </span></span>transcriptomic<span> profiling and explore the association between mast cells with clinical and biological features. In the study cohort (N = 60), H scores showed a significant moderate correlation with NanoString mast cell scores (</span></span><em>r</em> = 0.525; <em>P</em> < .001). Both H score and NanoString mast cell scores showed a significant positive correlation (<em>P</em> < .05) with head and neck location, nonepithelioid morphology, and lower tumor grade. Mast cell enrichment significantly correlated with higher NanoString regulatory T-cell scores (H score, <em>r</em> = 0.32; <em>P</em> = .01; NanoString mast cell score, <em>r</em> = 0.27; <em>P</em><span> = .04). NanoString mast cell scores positively correlated with signaling pathways relating to antigen presentation (</span><em>r</em> = 0.264; <em>P</em><span> = .0414) and negatively correlated with apoptosis (</span><em>r</em> = −0.366; <em>P</em> = .0040), DNA damage repair (<em>r</em> = −0.348; <em>P</em><span> = .0064), and cell proliferation (</span><em>r</em> = −0.542; <em>P</em> < .001). Interestingly, in the metastatic setting, patients with mast cell–enriched angiosarcoma showed poorer progression-free survival (median, 0.2 vs 0.4 years; hazard ratio = 3.05; <em>P</em> = .0489) along with a trend toward worse overall survival (median, 0.2 vs 0.6 years; hazard ratio, 2.86; <em>P</em> = .0574) compared with patients with mast cell–poor angiosarcoma. In conclusion, we demonstrated the presence of mast cells in human angiosarcoma and provided initial evidence of their potential clinical and biological significance. Future research will be required to elucidate their specific roles and mechanisms, which may uncover novel avenues for therapeutic intervention.</p></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":null,"pages":null},"PeriodicalIF":5.1000,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Laboratory Investigation","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0023683724000011","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Recent studies have described several molecular subtypes and deregulation of immuno-oncologic signaling pathways in angiosarcoma. Interestingly, mast cells were enriched in subsets of angiosarcoma, although their significance remains unknown. In this study, we aim to verify this observation using immunohistochemistry (H scores) and NanoString transcriptomic profiling and explore the association between mast cells with clinical and biological features. In the study cohort (N = 60), H scores showed a significant moderate correlation with NanoString mast cell scores (r = 0.525; P < .001). Both H score and NanoString mast cell scores showed a significant positive correlation (P < .05) with head and neck location, nonepithelioid morphology, and lower tumor grade. Mast cell enrichment significantly correlated with higher NanoString regulatory T-cell scores (H score, r = 0.32; P = .01; NanoString mast cell score, r = 0.27; P = .04). NanoString mast cell scores positively correlated with signaling pathways relating to antigen presentation (r = 0.264; P = .0414) and negatively correlated with apoptosis (r = −0.366; P = .0040), DNA damage repair (r = −0.348; P = .0064), and cell proliferation (r = −0.542; P < .001). Interestingly, in the metastatic setting, patients with mast cell–enriched angiosarcoma showed poorer progression-free survival (median, 0.2 vs 0.4 years; hazard ratio = 3.05; P = .0489) along with a trend toward worse overall survival (median, 0.2 vs 0.6 years; hazard ratio, 2.86; P = .0574) compared with patients with mast cell–poor angiosarcoma. In conclusion, we demonstrated the presence of mast cells in human angiosarcoma and provided initial evidence of their potential clinical and biological significance. Future research will be required to elucidate their specific roles and mechanisms, which may uncover novel avenues for therapeutic intervention.
期刊介绍:
Laboratory Investigation is an international journal owned by the United States and Canadian Academy of Pathology. Laboratory Investigation offers prompt publication of high-quality original research in all biomedical disciplines relating to the understanding of human disease and the application of new methods to the diagnosis of disease. Both human and experimental studies are welcome.