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Strong Correlation of Indoleamine 2,3-Dioxygenase 1 Expression with Basal-Like Phenotype and Increased Lymphocytic Infiltration in Triple-Negative Breast Cancer

Title
Strong Correlation of Indoleamine 2,3-Dioxygenase 1 Expression with Basal-Like Phenotype and Increased Lymphocytic Infiltration in Triple-Negative Breast Cancer
Authors
Kim, SewhaPark, SanghuiCho, Min SunLim, WoosungMoon, Byung-InSung, Sun Hee
Ewha Authors
성순희문병인조민선임우성박상희
SCOPUS Author ID
성순희scopus; 문병인scopus; 조민선scopus; 임우성scopus; 박상희scopus
Issue Date
2017
Journal Title
JOURNAL OF CANCER
ISSN
1837-9664JCR Link
Citation
vol. 8, no. 1, pp. 124 - 130
Keywords
triple negative breast carcinomamolecular subtypebasal-like phenotypeindoleamine 2,3-dioxygenase 1 (IDO1)immunohistochemistrytumor infiltrating lymphocyte (TIL).
Publisher
IVYSPRING INT PUBL
Indexed
SCIE; SCOPUS WOS scopus
Abstract
Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive enzyme involved in tumor immune escape. Blockade of the IDO1 pathway is an emerging modality of cancer immunotherapy. Triple-negative breast cancer (TNBC) lacks established therapeutic targets and may be a good candidate for this novel immunotherapeutic agent. The purpose of this study was to evaluate the clinicopathologic characteristics of the IDO1-expressing TNBC subset. A tissue microarray was constructed from 200 patients with TNBC. Immunohistochemistry (IHC) for IDO1 and TNBC molecular subtype-surrogate markers (AR, GCDFP-15, claudin-3, E-cadherin, CK5/ 6, and EGFR) was performed using this tissue microarray. Real-time polymerase chain reaction was performed to confirm the IDO1 mRNA expression level in 16 fresh-frozen TNBC samples. Two hundred TNBCs were classified into four subtypes based on surrogate IHC results: 22 luminal androgen receptor type (11.0%), 23 claudin-low type (11.4%), 103 basal-like type (51.5%), and 52 mixed type (26.0%). IDO1 positivity (defined as expression of > 10% tumor cells) was observed in 37% of all TNBCs. IDO1 IHC expression was well correlated with mRNA expression. IDO1 positivity was significantly associated with smaller tumor size, dense stromal lymphocytic infiltration, and basal-like phenotype; however, it did not affect the patients' prognosis. IDO1 expression in basal-like TNBCs is considered an immune inhibitory signal that counterbalances active immunity and may reflect the high mutational load of these tumors. Our results suggest which patients with TNBC would be more efficaciously treated with IDO1 blockade.
DOI
10.7150/jca.17437
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의학전문대학원 > 의학과 > Journal papers
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