title: S-phase fraction and ploidy as predictive markers in primary disease and recurrence of papillary thyroid carcinoma.
abstract: OBJECTIVE
  To investigate the prognostic influence of DNA ploidy and S-phase fraction (SPF) on disease-free (DFS) and overall survival (OS) of patients with primary disease and loco-regional lymph node recurrence of papillary thyroid carcinoma (PTC).
  
  
  METHODS
  A large prospective study with long-term follow-up (median, 117 months).
  
  
  METHODS
  Two series of patients with primary PTC (n = 305) and lymph node recurrence metastasis (LNM) (n = 39) were involved in the study.
  
  
  METHODS
  Patient's age and gender, histological variant, pathological tumour-node-metastasis (pTNM) staging, extrathyroidal extension, vascular and lymphatic invasion and tumour bilateral growth were the clinical and pathological characteristics evaluated. DNA flow cytometry was performed on fresh/frozen surgical tumour samples. Cox regression models were estimated for prognostic analyses.
  
  
  RESULTS
  Seventeen (5·6%) primary tumours and five (12·8%) LNMs were aneuploid, while mean SPF was 2·7% and 3·7%, respectively (P = 0·022). High SPF was significantly associated with lymphatic invasion and tall cell and diffuse sclerosing variants. In univariate analysis, all the clinico-pathological variables, but tumour bilateral growth and gender, were significantly correlated with survival. SPF showed borderline significance (P = 0·051) in relation to OS. In multivariate analysis, older age (≥48 years), lymph node spread and high SPF were significantly adverse prognostic factors. Extrathyroidal extension and distant metastasis for OS, as well as tumour size for DFS, were also found as unfavourable prognostic features. In LNM, the Kaplan-Meier curves showed significant differences for older age and DNA aneuploidy (recurrence; P = 0·011).
  
  
  CONCLUSIONS
  The results indicate that SPF and ploidy can provide additional predictive information in patients with PTC.
authors.affiliation: Serviço de Anatomia Patológicado, Instituto Português de Oncologia de Lisboa, EPE, Lisbon, Portugal. aepinto@ipolisboa.min-saude.pt
authors.forename: António E
authors.initials: AE
authors.lastname: Pinto
authors.forename: Giovani L
authors.initials: GL
authors.lastname: Silva
authors.forename: Teresa
authors.initials: T
authors.lastname: Pereira
authors.forename: Rafael A
authors.initials: RA
authors.lastname: Cabrera
authors.forename: Jorge Rosa
authors.initials: JR
authors.lastname: Santos
authors.forename: Valeriano
authors.initials: V
authors.lastname: Leite
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma; D002291:Carcinoma, Papillary; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D011003:Ploidies; D011446:Prospective Studies; D016196:S Phase; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000401:mortality; D055815:Young Adult