title: Cytoplasmic expression of high mobility group B1 (HMGB1) is associated with tumor-infiltrating lymphocytes (TILs) in breast cancer.
abstract: High mobility group box 1 (HMGB1) is a prototypic alarmin or damage-associated molecule inducing inflammatory mediator release and immune response. Several studies have revealed the prognostic and predictive importance of tumor-infiltrating lymphocytes (TILs) in breast cancer. The present study analyzed the expression of HMGB1 in each breast cancer subtype and the relationship between the expression level of HMGB1 and pathologic parameters including TILs. Two cohorts were studied: 575 consecutive breast cancer patients who underwent surgery between 1995 and 1998; and 767 triple negative breast cancer (TNBC) patients who underwent surgery between 2004 and 2010. The immunohistochemical expression level of HMGB1 in cytoplasm and nucleus was evaluated using tissue microarrays. High HMGB1 expression in cytoplasm was associated with high histologic grade, pT stage, and abundant TILs in the consecutive breast cancer cohort. Cytoplasmic HMGB1 expression was higher in TNBCs and HER2-positive tumors than in hormone receptor-positive tumors. In the TNBC cohort, high cytoplasmic HMGB1 expression was significantly associated with high histologic grade, abundant TILs, and high numbers of CD8+ cells. However, nuclear HMGB1 expression was not associated with histologic grade or TIL levels. Neither cytoplasmic nor nuclear expression of HMGB1 showed prognostic significance in TNBC. Cytoplasmic HMGB1 expression is associated with TIL levels in breast cancer.
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea.
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Pathology, BioMedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, 1-10 Ami-Dong, Seo-Gu, Busan, 602-739, South Korea.
authors.forename: Ahrong
authors.initials: A
authors.lastname: Kim
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea.
authors.forename: In Hye
authors.initials: IH
authors.lastname: Song
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea.
authors.forename: In Ah
authors.initials: IA
authors.lastname: Park
authors.affiliation: Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea.
authors.forename: Jong Han
authors.initials: JH
authors.lastname: Yu
authors.affiliation: Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea.
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Ahn
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea.
authors.forename: Gyungyub
authors.initials: G
authors.lastname: Gong
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002467:Cell Nucleus / Q000473:pathology; D015331:Cohort Studies; D003593:Cytoplasm / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D011379:Prognosis; D056910:Republic of Korea
chemical_list: D014408:Biomarkers, Tumor; D024243:HMGB1 Protein; C585491:HMGB1 protein, human
keywords: Breast cancer; HMGB1; Tumor infiltrating lymphocytes