title: Impact of pathognomonic genetic alterations on the prognosis of papillary thyroid carcinoma. ESES vienna presentation.
abstract: BACKGROUND
  BRAF mutations and RET or NTRK1 rearrangements were identified as causing events that drive the malignant transformation of the thyroid follicular cell. The impact of these alterations on the course of papillary thyroid carcinoma (PTC) is still unsettled.
  
  
  METHODS
  Tumor tissues of 290 (98 male, 192 female) patients were intra-operatively snap frozen or harvested from archival paraffin-embedded blocks and used for extraction of DNA and RNA. Comprehensive analysis of RET/PTC and NTRK1 rearrangements was carried out by multiplex screening RT-PCR, hybrid-specific RT-PCR and sequencing of detected hybrids. A mutation-specific PCR was used for BRAF analysis.
  
  
  RESULTS
  The BRAF V600E mutation was detected in 122/290 (42%), RET rearrangements in 20/137 (14.6%), and NTRK1 rearrangements in 15/93 (16.1%) PTCs. One hundred forty one out of 290 (48.6%) PTCs demonstrated none of the genetic alterations studied. Eight PTCs expressed two different mutations (1 RET/PTC + BRAF, 6 NTRK1 + BRAF, 1 RET/PTC + NTRK1). Tumor-specific survival analysis (mean follow-up, 5.5 years) demonstrated no significant difference, but a tendency toward worse prognosis of BRAF-positive patients compared to BRAF-negative patients or rearrangement-positive patients, respectively.
  
  
  CONCLUSIONS
  Long-term follow-up data on large tumor panels are needed to disclose significant survival differences of prognostic predictors on PTC. This study provides further evidence that patients harboring BRAF-V600E-positive PTCs may experience an unfavorable course of the disease compared to patients with tumors carrying other genetic alterations.
authors.affiliation: Endocrine Surgery, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55101 Mainz, Germany. musholt@uni-mainz.de
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Musholt
authors.forename: Sonja
authors.initials: S
authors.lastname: Schönefeld
authors.forename: Christina H
authors.initials: CH
authors.lastname: Schwarz
authors.forename: Felix M
authors.initials: FM
authors.lastname: Watzka
authors.forename: Petra B
authors.initials: PB
authors.lastname: Musholt
authors.forename: Christian
authors.initials: C
authors.lastname: Fottner
authors.forename: Matthias M
authors.initials: MM
authors.lastname: Weber
authors.forename: Erik
authors.initials: E
authors.lastname: Springer
authors.forename: Arno
authors.initials: A
authors.lastname: Schad
mesh_terms: D000231:Adenocarcinoma, Papillary / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D016009:Chi-Square Distribution; D015331:Cohort Studies; D005260:Female; D005629:Frozen Sections; D015321:Gene Rearrangement; D005858:Germany; D006801:Humans; D007430:Intraoperative Care / Q000379:methods; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D020917:Receptor, trkA / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D013965:Thyroidectomy / Q000379:methods / Q000401:mortality
chemical_list: D020917:Receptor, trkA; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf