RET protein expression has no prognostic impact on the long-term outcome of papillary thyroid carcinoma.
BACKGROUND
RET proto-oncogene rearrangements (RET/PTC) are causative events in the pathogenesis of a subset of papillary thyroid cancer (PTC). The prevalence of RET/PTC varies in different countries and according to specific clinical features: it is higher after radiation exposure and it is claimed to be higher in young patients. Conflicting results are reported regarding the prognostic role of RET/PTC activation.


OBJECTIVE
To investigate the prognostic meaning of RET/PTC rearrangement on the long term outcome of PTC.


METHODS
We have studied the expression of the RET encoded protein in 127 papillary thyroid carcinomas by immunohistochemistry using a polyclonal antibody against the tyrosine-kinase domain of the RET protein. These cases have been collected during 1970-1985, and have a mean (+/-S.D.) period of follow-up of 18.6+/-3.7 years (range 12-27 years). The results have been compared with the patients' outcome.


RESULTS
The tyrosine-kinase domain of RET was expressed in 82 (64.6%) papillary carcinomas. Among them, RET was highly expressed in 65 (51.2%) cases and moderately expressed in 17 (13.4%). RET expression was absent in 45 (35.4%) cases. No correlation was found between RET expression and other parameters such as sex, age at diagnosis, tumor class and histological variant. Follow-up analysis showed no influence of RET expression on patients' outcome. By multivariate analysis, age (>45 years) and tumor class IV, but not sex and RET expression were adverse prognostic indicators of death.


CONCLUSIONS
In conclusion, our analysis indicates that RET expression is frequently found in PTC, and has no influence on tumor outcome.
Basolo
F
F
Dipartimento di Oncologia, Universita di Pisa, Via Paradisa, 2, 56124 Pisa, Italy.
Molinaro
E
E
Agate
L
L
Pinchera
A
A
Pollina
L
L
Chiappetta
G
G
Monaco
C
C
Santoro
M
M
Fusco
A
A
Miccoli
P
P
Elisei
R
R
Capezzone
M
M
Pacini
F
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D002291:Carcinoma, Papillary / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D002648:Child; D029721:Drosophila Proteins; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; D013961:Thyroid Gland / Q000378:metabolism / Q000473:pathology; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology
D015415:Biomarkers; D029721:Drosophila Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila