Prognostic significance of RET and NTRK1 rearrangements in sporadic papillary thyroid carcinoma

Background. The expression of RET/PTC chimeras was demonstrated in 10% to 2 0% of sporadic papillary thyroid carcinomas (PTCs), whereas rearrangements of NTRK1 were detected less frequently. Some investigators have hypothesize d that RET/PTC activation is preferentially associated with, slow-growing t umors of low malignancy in elderly patients; other studies support the cont rary. Methods, Expression analysis of RET and NTRK1 reins performed by duplex rev erse transcription-polymerase chain reaction in tumor tissues from 119 pati ents 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 hTRK1 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 patie nts with RET/PTC chimeras, a statistically not significant tendency towards younger age, lower recurrence rate, and improved survival was observed, de spite increased incidence of lymph node metastasis. Cumulative survival ana lysis of NTRK1 rearrangement-positive individuals demonstrated a worse outc ome when compared with patients with expression of RET hybrids (P =.055). Conclusions. The high incidence of yet uncharacterized NTRK1 hybrid mRNAs i n our patient cohort leads to the speculation that activating chromosomal r earrangements 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.