Surgery · 2020
Prevalence and clinical relevance of tumor-associated tissue eosinophilia (TATE) in breast cancer.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод пока не подготовлен
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Chouliaras Konstantinos, Tokumaru Yoshihisa, Asaoka Mariko, Oshi Masanori, Attwood Kristopher M, Yoshida Kazuhiro, Ishikawa Takashi, Takabe Kazuaki
Аннотация
BACKGROUND: Tumor-associated tissue eosinophilia (TATE) has been associated with outcomes in a variety of solid tumors; however, its role in breast cancer is not well defined. We hypothesized that tumor-associated tissue eosinophilia is associated with a high mutation and neoantigen load, and we assessed its correlation with cancer outcomes.
METHODS: The Cancer Genome Atlas was analyzed for eosinophil signatures in breast cancer specimens. Descriptive analyses were performed, including the tumor-infiltrating cell composition using CIBERSORT, cytolytic activity score, and gene set enrichment analysis. Overall survival and disease-free survival were calculated using the Kaplan-Meier method.
RESULTS: Out of 1069 cases analyzed, 40 (3.7%) had tissue eosinophils (the tumor-associated tissue eosinophilia group). Tumor-associated tissue eosinophilia was noted in 32.5% luminal, 5% HER2-positive, and 15% triple-negative breast cancer subtypes. The single nucleotide variant-neoantigen load was significantly higher in the tumor-associated tissue eosinophilia group (P = .005), with a higher nonsilent mutation rate (P = .01). The tumor-associated tissue eosinophilia group had lower cytolytic activity (P = .02) but had enriched MYC-targeted (P = .002), E2F-targeted (P = .04), deoxyribonucleic acid repair (P = .03), and unfolded protein response gene sets (P = .05). Tumor-associated tissue eosinophilia was associated with a trend toward improved disease-free survival (P = .06) but presented no differences in overall survival (P = .56).
CONCLUSION: Tumor-associated tissue eosinophilia was noted in 3.7% of breast cancers and was associated with a higher single nucleotide variant-neoantigen load and nonsilent mutation rate, similar to that of tumor-infiltrating lymphocytes in the triple-negative subtype. However, a lower cytolytic activity score and enriched cell proliferation-related gene sets implicate different roles for tumor-associated tissue eosinophilia than for tumor-infiltrating lymphocytes.
METHODS: The Cancer Genome Atlas was analyzed for eosinophil signatures in breast cancer specimens. Descriptive analyses were performed, including the tumor-infiltrating cell composition using CIBERSORT, cytolytic activity score, and gene set enrichment analysis. Overall survival and disease-free survival were calculated using the Kaplan-Meier method.
RESULTS: Out of 1069 cases analyzed, 40 (3.7%) had tissue eosinophils (the tumor-associated tissue eosinophilia group). Tumor-associated tissue eosinophilia was noted in 32.5% luminal, 5% HER2-positive, and 15% triple-negative breast cancer subtypes. The single nucleotide variant-neoantigen load was significantly higher in the tumor-associated tissue eosinophilia group (P = .005), with a higher nonsilent mutation rate (P = .01). The tumor-associated tissue eosinophilia group had lower cytolytic activity (P = .02) but had enriched MYC-targeted (P = .002), E2F-targeted (P = .04), deoxyribonucleic acid repair (P = .03), and unfolded protein response gene sets (P = .05). Tumor-associated tissue eosinophilia was associated with a trend toward improved disease-free survival (P = .06) but presented no differences in overall survival (P = .56).
CONCLUSION: Tumor-associated tissue eosinophilia was noted in 3.7% of breast cancers and was associated with a higher single nucleotide variant-neoantigen load and nonsilent mutation rate, similar to that of tumor-infiltrating lymphocytes in the triple-negative subtype. However, a lower cytolytic activity score and enriched cell proliferation-related gene sets implicate different roles for tumor-associated tissue eosinophilia than for tumor-infiltrating lymphocytes.