title: Revisiting the transcriptional analysis of primary tumours and associated nodal metastases with enhanced biological and statistical controls: application to thyroid cancer.
abstract: BACKGROUND
  Transcriptome profiling has helped characterise nodal spread. The interpretation of these data, however, is not without ambiguities.
  
  
  METHODS
  We profiled the transcriptomes of papillary thyroid cancer nodal metastases, associated primary tumours and primary tumours from N0 patients. We also included patient-matched non-cancerous thyroid and lymph node samples as controls to address some limits of previous studies.
  
  
  RESULTS
  The transcriptomes of patient-matched primary tumours and metastases were more similar than those of unrelated metastases/primary pairs, as previously reported in other organ systems. This similarity partly reflected patient background. Lymphoid tissues in the metastases confounded the comparison of patient-matched primary tumours and metastases. We circumvented this with an original data adjustment, revealing a differential expression of stroma-related gene signatures also regulated in other organs. The comparison of N0 vs N+ primary tumours uncovered a signal irreproducible across independent data sets. This signal was also detectable when comparing the non-cancerous thyroid tissues adjacent to N0 and N+ tumours, suggesting a cohort-specific bias also likely present in previous similarly sized studies. Classification of N0 vs N+ yielded an accuracy of 63%, but additional statistical controls absent in previous studies revealed that this is explainable by chance alone. We used large data sets from The Cancer Genome Atlas: N0 vs N+ classification was not better than random for most cancers. Yet, it was significant, but of limited accuracy (<70%) for thyroid, breast and head and neck cancers.
  
  
  CONCLUSIONS
  The clinical potential of gene expression to predict nodal metastases seems limited for most cancers.
authors.affiliation: IRIBHM, Université Libre de Bruxelles (ULB), Route de Lennik, 808-1070 Brussels, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Tarabichi
authors.affiliation: IRIBHM, Université Libre de Bruxelles (ULB), Route de Lennik, 808-1070 Brussels, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Saiselet
authors.affiliation: Department of General and Digestive Surgery and Pathology, Pitié-Salpêtrière Hospital, Université Pierre and Marie Curie, 47-83, boulevard de l'Hôpital, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Trésallet
authors.affiliation: Department of General and Digestive Surgery and Pathology, Pitié-Salpêtrière Hospital, Université Pierre and Marie Curie, 47-83, boulevard de l'Hôpital, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Hoang
authors.affiliation: Department of Pathology, Jules Bordet Institute, Université Libre de Bruxelles (ULB), Boulevard de Waterloo, 125-1000 Brussels, Belgium.
authors.forename: D
authors.initials: D
authors.lastname: Larsimont
authors.affiliation: Thoracic Surgery, Jules Bordet Institute, Université Libre de Bruxelles (ULB), Boulevard de Waterloo, 125-1000 Brussels, Belgium.
authors.forename: G
authors.initials: G
authors.lastname: Andry
authors.affiliation: 1] IRIBHM, Université Libre de Bruxelles (ULB), Route de Lennik, 808-1070 Brussels, Belgium [2] WELBIO, Route de Lennik, 808-1070 Brussels, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Maenhaut
authors.affiliation: IRIBHM, Université Libre de Bruxelles (ULB), Route de Lennik, 808-1070 Brussels, Belgium.
authors.forename: V
authors.initials: V
authors.lastname: Detours
mesh_terms: D016022:Case-Control Studies; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D016609:Neoplasms, Second Primary / Q000235:genetics / Q000473:pathology; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology*; D059467:Transcriptome