Ret/PTC activation does not influence clinical and pathological features of adult papillary thyroid carcinomas.
OBJECTIVE
RET proto-oncogene rearrangements (ret/PTCs) represent the most common genetic alterations found in papillary thyroid carcinomas (PTCs). Correlation of ret/PTC expression with clinical outcome is controversial. The aim of the present study was to analyze the frequency of RET rearrangements in adult PTCs, and to investigate if ret/PTCs influence biological behavior and clinical features of the cancers.


METHODS
Ret/PTC rearrangements were looked for in tIssue samples of 48 PTCs collected at our institution. Data about clinical and pathological features of the tumors were also reviewed. Three separate association analyses were carried out on the cohort evaluating the effects of, respectively, ret/PTC positivity, preferential RET tyrosine kinase domain (RET-TK) expression, and ret/PTC plus RET-TK positivity, on age, sex, tumor size, staging, number of neoplastic foci, and histological subtype.


METHODS
The genetic study was conducted with the RT-PCR-Southern blot technique. Standard Student's t-test and Fisher exact test were applied for the association analyses.


RESULTS
The molecular genetic study demonstrated the positivity of ret/PTC1 and ret/PTC3 in 13 of 48 tumors (27.1%), and an exclusive or preferential RET-TK expression in 17 cases (35.4%). None of the three genetico-clinical analyses showed any significant association between ret/PTC expression and the clinical and pathological features of the cancers.


CONCLUSIONS
These data indicate that RET rearrangements may not play any distinctive role in driving histotype development and cancer progression in these neoplasms. Moreover, they weaken the possibility of using ret/PTC as a prognostic marker for papillary thyroid carcinomas.
Puxeddu
Efisio
E
Department of Internal Medicine, Division of Internal Medicine and Endocrine and Metabolic Science, University of Perugia, via E. del Pozzo, 06126 Perugia, Italy. efisio@dimisem.med.unipg.it
Moretti
Sonia
S
Giannico
Angela
A
Martinelli
Marco
M
Marino
Cecilia
C
Avenia
Nicola
N
Cristofani
Roberto
R
Farabi
Raffaele
R
Reboldi
Gianpaolo
G
Ribacchi
Rodolfo
R
Pontecorvi
Alfredo
A
Santeusanio
Fausto
F
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002291:Carcinoma, Papillary / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D015331:Cohort Studies; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D008297:Male; D008875:Middle Aged; D008967:Molecular Biology; D056918:Nuclear Receptor Coactivators; D015513:Oncogene Proteins / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000378:metabolism; D011505:Protein-Tyrosine Kinases; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D014157:Transcription Factors
C000715470:MAS1 protein, human; C111382:NCOA4 protein, human; D056918:Nuclear Receptor Coactivators; D015513:Oncogene Proteins; D015514:Oncogene Proteins, Fusion; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D011505:Protein-Tyrosine Kinases; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C093573:ret-PTC fusion oncoproteins, human