Impact of pathognomonic genetic alterations on the prognosis of papillary thyroid carcinoma. ESES vienna presentation.
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.
Musholt
Thomas J
TJ
Endocrine Surgery, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55101 Mainz, Germany. musholt@uni-mainz.de
Schönefeld
Sonja
S
Schwarz
Christina H
CH
Watzka
Felix M
FM
Musholt
Petra B
PB
Fottner
Christian
C
Weber
Matthias M
MM
Springer
Erik
E
Schad
Arno
A
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
D020917:Receptor, trkA; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf