title: Predictive Value of Tertiary Lymphoid Structures Assessed by High Endothelial Venule Counts in the Neoadjuvant Setting of Triple-Negative Breast Cancer.
abstract: OBJECTIVE
  The tertiary lymphoid structure (TLS) is an important source of tumor-infiltrating lymphocytes (TILs), which have a strong prognostic and predictive value in triple-negative breast cancer (TNBC). A previous study reported that the levels ofCXCL13mRNA expression were associated with TLSs, but measuring the gene expression is challenging in routine practice. Therefore, this study evaluated the MECA79-positive high endothelial venule (HEV) densities and their association with the histopathologically assessed TLSs in biopsy samples. In addition, the relationship of TLSs with theCXCL13transcript levels and clinical outcomes were examined.
  
  
  METHODS
  A total of 108 TNBC patients treated with neoadjuvant chemotherapy (NAC) were studied. The amounts of TILs and TLSs were measured histopathologically using hematoxylin and eosin-stained slides. The HEV densities and TIL subpopulations were measured by immunohistochemistry for MECA79, CD3, CD8, and CD20.CXCL13mRNA expression levels using a NanoString assay (NanoString Technologies).
  
  
  RESULTS
  The mean number of HEVs in pre-NAC biopsies was 12 (range, 0 to 72). The amounts of TILs and TLSs, HEV density, andCXCL13expression showed robust correlations with each other. A lower pre-NAC clinical T stage, higher TIL and TLS levels, a higher HEV density, CD20-positive cell density, andCXCL13expression were significant predictors of a pathologic complete response (pCR). Higher CD8-positive cell density and levels ofCXCL13expression were significantly associated with a better disease-free survival rate.
  
  
  CONCLUSIONS
  MECA79-positive HEV density in pre-NAC biopsies is an objective and quantitative surrogate marker of TLS and might be a valuable tool for predicting pCR of TNBC in routine pathology practice.
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: In Hye
authors.initials: IH
authors.lastname: Song
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.|Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Heo
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Won Seon
authors.initials: WS
authors.lastname: Bang
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Hye Seon
authors.initials: HS
authors.lastname: Park
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: In Ah
authors.initials: IA
authors.lastname: Park
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.|Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Young-Ae
authors.initials: YA
authors.lastname: Kim
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Suk Young
authors.initials: SY
authors.lastname: Park
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Jin
authors.initials: J
authors.lastname: Roh
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Gyungyub
authors.initials: G
authors.lastname: Gong
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D001706:Biopsy; D003131:Combined Modality Therapy; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008207:Lymphatic Metastasis; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D000072717:Tertiary Lymphoid Structures / Q000276:immunology / Q000473:pathology*; D064726:Triple Negative Breast Neoplasms / Q000276:immunology / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: Immunohistochemistry; Prognosis; Tertiary lymphoid structure; Triple-negative breast neoplasms