title: Tertiary lymphoid structures: prognostic significance and relationship with tumour-infiltrating lymphocytes in triple-negative breast cancer.
abstract: BACKGROUND
  Tumour-infiltrating lymphocytes (TILs) have a strong prognostic significance, particularly in triple-negative breast cancer (TNBC). One important source of TILs in breast cancer is tertiary lymphoid structures (TLSs).
  
  
  OBJECTIVE
  To carry out a histological analysis of surgically resected TNBC to identify the location of TLSs, the relationship between TLSs and TILs and their prognostic significance in TNBC.
  
  
  METHODS
  We retrospectively analysed 769 patients with TNBC.
  
  
  RESULTS
  TILs were defined as the percentage of stroma of invasive carcinoma infiltrated by lymphocytes. TLSs were mainly present within adjacent terminal duct lobular units and around in situ components. TNBC with higher levels of TILs showed a higher nuclear grade, lower lymphovascular invasion, less accompanying in situ component, a homogeneous growth pattern, necrosis in invasive areas, low levels of tumour stroma, high levels of peritumoral lymphocytic infiltration and moderate to abundant TLSs in adjacent tissue. TILs, the degree of peritumoral lymphocytic infiltration and adjacent TLSs were prognostic factors for disease-free and overall survival. Although the TIL level did not have a prognostic value in stage I, it added significant prognostic information for stages II and III. Conversely, patients with high levels of TILs did not show prognostic differences according to the pTNM stage. Patients with high levels of TILs (> 60%) and moderate to abundant TLSs had significantly better disease-free survival than those with high levels of TILs but none or few TLSs.
  
  
  CONCLUSIONS
  TLSs are frequently present in TNBC and are closely associated with TILs. TILs provide additional prognostic information in patients with TNBC with a higher pTNM stage.
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
authors.forename: In Ah
authors.initials: IA
authors.lastname: Park
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
authors.forename: In Hye
authors.initials: IH
authors.lastname: Song
authors.affiliation: Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Shin
authors.affiliation: Department of Pathology, Korea University of Anam Hospital, Korea University College of Medicine, Seoul, Korea.
authors.forename: Joo Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
authors.forename: Jong Han
authors.initials: JH
authors.lastname: Yu
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
authors.forename: Gyungyub
authors.initials: G
authors.lastname: Gong
mesh_terms: D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology*; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D064726:Triple Negative Breast Neoplasms / Q000473:pathology* / Q000628:therapy; D055815:Young Adult
keywords: BREAST CANCER; HISTOPATHOLOGY; TUMOUR IMMUNITY