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

Abstract

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.

• Authors: T J Musholt, P B Musholt, N Khaladj, D Schulz, G F Scheumann, J Klempnauer
• Journal: Surgery (Surgery) Vol. 128 Issue 6 Pg. 984-93 (Dec 2000) ISSN: 0039-6060 [Print] United States
• PMID: 11114633 (Publication Type: Journal Article)

Chemical References

• Drosophila Proteins
• Proto-Oncogene Proteins
• RNA, Messenger
• Proto-Oncogene Proteins c-ret
• Receptor Protein-Tyrosine Kinases
• Receptor, trkA
• Ret protein, Drosophila

Topics

• Carcinoma, Papillary (genetics, mortality)
• Drosophila Proteins
• Female
• Gene Rearrangement
• Humans
• Male
• Prognosis
• Proto-Oncogene Proteins (genetics)
• Proto-Oncogene Proteins c-ret
• RNA, Messenger (analysis)
• Receptor Protein-Tyrosine Kinases (genetics)
• Receptor, trkA (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Thyroid Neoplasms (genetics, mortality)