title: Tertiary lymphoid structures are associated with higher tumor grade in primary operable breast cancer patients.
abstract: BACKGROUND
  Tertiary lymphoid structures (TLS) are highly organized immune cell aggregates that develop at sites of inflammation or infection in non-lymphoid organs. Despite the described role of inflammation in tumor progression, it is still unclear whether the process of lymphoid neogenesis and biological function of ectopic lymphoid tissue in tumors are beneficial or detrimental to tumor growth. In this study we analysed if TLS are found in human breast carcinomas and its association with clinicopathological parameters.
  
  
  METHODS
  In a patient group (n = 290) who underwent primary surgery between 2011 and 2012 we assessed the interrelationship between the presence of TLS in breast tumors and clinicopathological factors. Prognostic factors were entered into a binary logistic regression model for identifying independent predictors for intratumoral TLS formation.
  
  
  RESULTS
  There was a positive association between the grade of immune cell infiltration within the tumor and important prognostic parameters such as hormone receptor status, tumor grade and lymph node involvement. The majority of patients with high grade infiltration of immune cells had TLS positive tumors. In addition to the degree of immune cell infiltration, the presence of TLS was associated with organized immune cell aggregates, hormone receptor status and tumor grade. Tumors with histological grade 3 were the strongest predictor for the presence of TLS in a multivariate regression model. The model also predicted that the odds for having intratumoral TLS formation were ten times higher for patients with high grade of inflammation than low grade.
  
  
  CONCLUSIONS
  Human breast carcinomas frequently contain TLS and the presence of these structures is associated with aggressive forms of tumors. Locally generated immune response with potentially antitumor immunity may control tumorigenesis and metastasis. Thus, defining the role of TLS formation in breast carcinomas may lead to alternative therapeutic approaches targeting the immune system.
authors.affiliation: RNA and Molecular Pathology Research Group, Department of Medical Biology, Faculty of Health Sciences, University of Tromso, N-9037, Tromso, Norway. stine.l.figenschau@uit.no.
authors.forename: Stine L
authors.initials: SL
authors.lastname: Figenschau
authors.affiliation: Department of Pathology, University Hospital of North Norway, N-9038, Tromso, Norway. silje.fismen@unn.no.
authors.forename: Silje
authors.initials: S
authors.lastname: Fismen
authors.affiliation: RNA and Molecular Pathology Research Group, Department of Medical Biology, Faculty of Health Sciences, University of Tromso, N-9037, Tromso, Norway. kristin.fenton@uit.no.
authors.forename: Kristin A
authors.initials: KA
authors.lastname: Fenton
authors.affiliation: The Microarray Platform, Faculty of Health Sciences, University of Tromso, N-9037, Tromso, Norway. christopher.fenton@uit.no.
authors.forename: Christopher
authors.initials: C
authors.lastname: Fenton
authors.affiliation: RNA and Molecular Pathology Research Group, Department of Medical Biology, Faculty of Health Sciences, University of Tromso, N-9037, Tromso, Norway. elin.s.mortensen@uit.no.|Department of Pathology, University Hospital of North Norway, N-9038, Tromso, Norway. elin.s.mortensen@uit.no.
authors.forename: Elin S
authors.initials: ES
authors.lastname: Mortensen
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D001706:Biopsy; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology*; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D047368:Tumor Burden; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor