title: Anaplastic thyroid cancer evolved from papillary carcinoma: demonstration of anaplastic transformation by means of the inter-simple sequence repeat polymerase chain reaction.
abstract: BACKGROUND
  In thyroid tumors, the coexistence of well- and poorly differentiated tumor types has led to the hypothesis that poorly differentiated thyroid tumors develop from well-differentiated thyroid tumors. By evaluating the genomic instability of histologically distinct but coexisting tumor foci, this study aimed to develop an improved understanding of thyroid tumorigenesis and tumor evolution.
  
  
  METHODS
  Laser capture microdissection (LCM) was carried out on archival formalin-fixed, paraffin-embedded sections from a tumor containing foci of classic papillary thyroid cancer and anaplastic thyroid cancer. DNA was extracted from each microdissected tumor focus. In addition, cryopreserved bulk normal and neoplastic thyroid tissue underwent DNA extraction. All DNA samples were subsequently evaluated for genomic instability by means of inter-simple sequence repeat polymerase chain reaction.
  
  
  RESULTS
  The LCM DNA from each archival paraffin-embedded tumor focus demonstrated unique patterns of banding as compared with the cryopreserved tumor and normal tissue DNA. Thus, intratumoral variability in genomic instability was observed. Comparison of inter-simple sequence repeat polymerase chain reaction patterns of LCM DNA from adjacent foci of papillary and anaplastic tumors showed conserved genome alterations.
  
  
  CONCLUSIONS
  At the genome level, thyroid tumors may be highly heterogeneous. The intratumoral histologic heterogeneity observed in thyroid neoplasms reflects genetically heterogeneous underlying tumor cell populations that are demonstrated by the observed differences in their rates and extents of genomic instability. The conserved genomic alterations in the microdissected papillary and anaplastic foci suggest intratumoral evolution, with transformation of a preexisting papillary tumor to anaplastic carcinoma.
authors.affiliation: Department of Head and neck Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Sam M
authors.initials: SM
authors.lastname: Wiseman
authors.forename: Thom R
authors.initials: TR
authors.lastname: Loree
authors.forename: Wesley L
authors.initials: WL
authors.lastname: Hicks
authors.forename: Nestor R
authors.initials: NR
authors.lastname: Rigual
authors.forename: Janet S
authors.initials: JS
authors.lastname: Winston
authors.forename: Donfeng
authors.initials: D
authors.lastname: Tan
authors.forename: Garth R
authors.initials: GR
authors.lastname: Anderson
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Stoler
mesh_terms: D000368:Aged; D001932:Brain Neoplasms / Q000556:secondary; D002277:Carcinoma / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000556:secondary / Q000601:surgery; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D004210:Dissection / Q000379:methods; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D016133:Polymerase Chain Reaction / Q000379:methods*; D013964:Thyroid Neoplasms / Q000473:pathology* / Q000601:surgery