title: CD8+ tumour-infiltrating lymphocytes and COX2 expression may predict relapse in differentiated thyroid cancer.
abstract: OBJECTIVE
  There is an increasing rate of papillary thyroid carcinomas that may never progress to cause symptoms or death. Predicting outcome and determining tumour aggressiveness could help diminish the number of patients submitted to aggressive treatments. We aimed to evaluate whether markers of the immune system response and of tumour-associated inflammation could predict outcome of differentiated thyroid cancer (DTC) patients.
  
  
  METHODS
  Retrospective cohort study.
  
  
  METHODS
  We studied 399 consecutive patients, including 325 papillary and 74 follicular thyroid carcinomas.
  
  
  METHODS
  Immune cell markers were evaluated using immunohistochemistry, including tumour-associated macrophages (CD68) and subsets of tumour-infiltrating lymphocytes (TIL), such as CD3, CD4, CD8, CD16, CD20, CD45RO, GRANZYME B, CD69 and CD25. We also investigated the expression of cyclooxygenase 2 (COX2) in tumour cells and the presence of concurrent lymphocytic infiltration characterizing chronic thyroiditis.
  
  
  RESULTS
  Concurrent lymphocytic infiltration characterizing chronic thyroiditis was observed in 29% of the cases. Among all the immunological parameters evaluated, only the enrichment of CD8+ lymphocytes (P = 0·001) and expression of COX2 (P =0·01) were associated with recurrence. A multivariate model analysis identified CD8+ TIL/COX2 as independent risk factor for recurrence. A multivariate analysis using Cox's proportional-hazards model adjusted for the presence of concurrent chronic thyroiditis demonstrated that the presence of concurrent chronic thyroiditis had no effect on prognostic prediction mediated by CD8+ TIL and COX2.
  
  
  CONCLUSIONS
  In conclusion, we suggest the use of a relatively simple pathology tool to help select cases that may benefit of a more aggressive approach sparing the majority of patients from unnecessary procedures.
authors.affiliation: Laboratory of Cancer Molecular Genetics, Faculty of Medical Sciences - University of Campinas (Unicamp), Campinas, Brazil.
authors.forename: Lucas Leite
authors.initials: LL
authors.lastname: Cunha
authors.affiliation: Laboratory of Cancer Molecular Genetics, Faculty of Medical Sciences - University of Campinas (Unicamp), Campinas, Brazil.
authors.forename: Marjory Alana
authors.initials: MA
authors.lastname: Marcello
authors.affiliation: Adolfo Lutz Institute, São Paulo, Brazil.
authors.forename: Suely
authors.initials: S
authors.lastname: Nonogaki
authors.affiliation: Laboratory of Cancer Molecular Genetics, Faculty of Medical Sciences - University of Campinas (Unicamp), Campinas, Brazil.|Department of Biological and Health Sciences, State University of Roraima, Boa Vista, Brazil.
authors.forename: Elaine Cristina
authors.initials: EC
authors.lastname: Morari
authors.affiliation: Department of Pathology, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Fernando Augusto
authors.initials: FA
authors.lastname: Soares
authors.affiliation: Department of Pathology, AC Camargo Cancer Center, São Paulo, Brazil.|Laboratory of Investigative and Molecular Pathology (Ciped), Faculty of Medical Sciences - University of Campinas (Unicamp), Campinas, Brazil.
authors.forename: José
authors.initials: J
authors.lastname: Vassallo
authors.affiliation: Laboratory of Cancer Molecular Genetics, Faculty of Medical Sciences - University of Campinas (Unicamp), Campinas, Brazil.
authors.forename: Laura Sterian
authors.initials: LS
authors.lastname: Ward
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000097:blood* / Q000276:immunology / Q000473:pathology; D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D002277:Carcinoma / Q000097:blood* / Q000276:immunology / Q000473:pathology; D002291:Carcinoma, Papillary; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D050031:Hashimoto Disease / Q000097:blood / Q000276:immunology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000097:blood* / Q000276:immunology / Q000473:pathology; D013966:Thyroiditis / Q000503:physiopathology
chemical_list: D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human