RET/PTC rearrangement is prevalent in follicular Hürthle cell carcinomas.
OBJECTIVE
The molecular alterations underlying follicular Hürthle cell carcinomas (FHCCs) are largely unknown. In an attempt to clarify this issue, we analysed a series of Hürthle cell tumours for the presence of RET/PTC and PAX8/PPARG rearrangements and BRAF, HRAS and NRAS mutations.


RESULTS
We investigated a series of 20 follicular Hürthle cell tumours [17 FHCCs and three follicular Hürthle cell adenomas (FHCAs)]. RET/PTC rearrangements were found in 33% of FHCAs and in 38% of FHCCs. All RET/PTC-positive FHCCs had a solid pattern of growth. PAX8/PPARG rearrangement was present in 27% of the FHCCs which displayed, in most cases, a follicular architecture. NRAS mutation was detected in one FHCC. An FHCC with a solid/microfollicular growth pattern scored positive for both RET/PTC and PAX8/PPARG rearrangement.


CONCLUSIONS
Our study has shown a significant association between RET/PTC rearrangements and FHCCs with a solid growth pattern, thus raising the possibility of using tyrosine kinase inhibitors for the treatment of patients with FHCCs, which are often refractory to radioiodine treatment.
Department of Genetics, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
Margriet M
MM
de Vries
Ricardo
R
Celestino
Patricia
P
Castro
Catarina
C
Eloy
Valdemar
V
Máximo
Jacqueline E
JE
van der Wal
John T M
JT
Plukker
Thera P
TP
Links
Robert M W
RM
Hofstra
Manuel
M
Sobrinho-Simões
Paula
P
Soares
D018249:Adenoma, Oxyphilic / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D015321:Gene Rearrangement; D011905:Genes, ras; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
D015514:Oncogene Proteins, Fusion; C551995:PAX8-PPARgamma fusion protein, human; D011505:Protein-Tyrosine Kinases; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; C093573:ret-PTC fusion oncoproteins, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)