Prognostic significance of RET and NTRK1 rearrangements in sporadic papillary thyroid carcinoma.
BACKGROUND
The expression of RET/PTC chimeras was demonstrated in 10% to 20% of sporadic papillary thyroid carcinomas (PTCs), whereas rearrangements of NTRK1 were detected less frequently. Some investigators have hypothesized that RET/PTC activation is preferentially associated with slow-growing tumors of low malignancy in elderly patients; other studies support the contrary.


METHODS
Expression analysis of RET and NTRK1 was performed by duplex reverse transcription-polymerase chain reaction in tumor tissues from 119 patients with PTC. Samples with suspected rearrangements were further analyzed for the expression of the hybrid messenger RNAs RET/PTC 1 to RET/PTC 7 and for known NTRK1 chimeras, respectively.


RESULTS
Seventeen of 119 tumors (14.3%) revealed somatic rearrangements of RET; NTRK1-derived hybrids were demonstrated in 15 cases (12.6%). In patients with RET/PTC chimeras, a statistically not significant tendency towards younger age, lower recurrence rate, and improved survival was observed, despite increased incidence of lymph node metastasis. Cumulative survival analysis of NTRK1 rearrangement-positive individuals demonstrated a worse outcome when compared with patients with expression of RET hybrids (P =.055).


CONCLUSIONS
The high incidence of yet uncharacterized NTRK1 hybrid mRNAs in our patient cohort leads to the speculation that activating chromosomal rearrangements of several tyrosine kinase receptors may be a common feature of PTCs and that the expression of distinct chimeras may potentially be of prognostic significance.
Musholt
T J
TJ
Department of Visceral and Transplantation Surgery, Hannover University Medical School, Hannover, Germany.
Musholt
P B
PB
Khaladj
N
N
Schulz
D
D
Scheumann
G F
GF
Klempnauer
J
J
D002291:Carcinoma, Papillary / Q000235:genetics* / Q000401:mortality; D029721:Drosophila Proteins; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D008297:Male; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D012333:RNA, Messenger / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D020917:Receptor, trkA / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000401:mortality
D029721:Drosophila Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA; C416649:Ret protein, Drosophila