title: CD8(+) tumor-infiltrating lymphocytes contribute to spontaneous "healing" in HER2-positive ductal carcinoma in situ.
abstract: We evaluated the associations between tumor-infiltrating lymphocytes (TIL) including CD8-positive [+] lymphocytes in ductal carcinoma in situ (DCIS) and histopathologic factors, particularly spontaneous "healing" and immunohistochemical (IHC)-based subtypes, to clarify the effects of host immune response to cancer cells proliferation during early carcinogenesis for the breast cancer. This cohort enrolled 82 DCIS patients. We examined the relationships between clinicopathologic factors including age, DCIS architecture, Van Nuys classification, grade, comedo necrosis, apocrine features, TIL, CD8(+) lymphocytes, healing, estrogen receptor and HER2 positivity, and IHC-based subtypes [luminal, luminal-HER2, HER2-positive, triple negative (TN)]. The results were analyzed by univariate and multivariate analyses. High numbers of TIL (high-TIL) and healing were seen in 30.5% and 39.0% of the cohort, respectively. The distributions of luminal, luminal-HER2, HER2 and TN subtypes were 73.2%, 9.8%, 13.4%, and 3.6%, respectively. High Van Nuys grading, high-grade, comedo necrosis, apocrine features, high-TIL, high CD8(+) lymphocytes and healing were significantly associated with HER2-positive (luminal-HER2, HER2), and TN subtypes. High-TIL was significantly associated with high-grade, comedo necrosis, apocrine features, healing, high CD8(+) lymphocytes and HER2 and TN subtypes. Healing was significantly correlated with high CD8(+) lymphocytes, high-grade, comedo necrosis, apocrine features, and HER2-positive and TN subtypes. Logistic regression analysis revealed a strong association between healing and TIL (odds ratio: 11.72, P = 0.024). High CD8(+) lymphocytes was also significantly associated with healing (odds ratio: 9.26, P = 0.009). The results of this study suggested that the spontaneous healing phenomenon might be induced by CD8(+) high-TIL associated with high-grade, comedo necrosis, apocrine features and HER2-positive DCIS.
authors.affiliation: Department of Pathology and Laboratory Medicine, Kurume University Medical Center, Kurume, Fukuoka, Japan.|Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.|Department of Surgery, Japan Community Health Care Organization Kurume General Hospital, Kurume, Fukuoka, Japan.
authors.forename: Michi
authors.initials: M
authors.lastname: Morita
authors.affiliation: Department of Pathology and Laboratory Medicine, Kurume University Medical Center, Kurume, Fukuoka, Japan.|Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Rin
authors.initials: R
authors.lastname: Yamaguchi
authors.affiliation: Department of Surgery, Japan Community Health Care Organization Kurume General Hospital, Kurume, Fukuoka, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Gary M
authors.initials: GM
authors.lastname: Tse
authors.affiliation: Department of Surgery, Japan Community Health Care Organization Kurume General Hospital, Kurume, Fukuoka, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Yamaguchi
authors.affiliation: Department of Pathology, Kawasaki Medical School, Kurashiki, Okayama, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kanomata
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Naito
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Akiba
authors.affiliation: Department of Biostatistics Center, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hattori
authors.affiliation: Department of Surgery, Nagasaki Harbor Medical Center City Hospital, Nagasaki, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Minami
authors.affiliation: Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Eguchi
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Yano
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor; D001706:Biopsy; D001943:Breast Neoplasms / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000209:etiology* / Q000473:pathology* / Q000628:therapy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism*; D008875:Middle Aged; D060787:Neoplasm Grading; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases
keywords: CD8+ tumor-infiltrating lymphocyte; DCIS; HER2; healing; regression