Activation of ret/PTC-1 has been documented in a minority of papillary thyr
oid carcinomas (PTC). In a recent study, the authors' group detected the pr
esence of ret/PTC-1 in association with a background of florid lymphocytic
thyroiditis (LT) in 58% of cases of PTC studied, which prompted them to exa
mine the incidence of RET/PTC-1 expression in 27 examples of various forms
of nonlymphomatous lymphoid infiltration of the thyroid by using TaqMan RT-
PCR. Overall, 21 cases (78%) were found to express the chimeric transcript
of ret/PTC-1. Eighteen cases of Hashimoto thyroiditis were positive (95%),
and, of these, three had concomitant PTC while the remainder had no histolo
gic evidence of associated malignancy. Three cases of lymphocytic thyroidit
is demonstrated activated ret/PTC-1 (43%), two having associated PTC. These
data suggest either that ret/PTC-1 is an indicator of follicular thyroid c
ell activation or that ret/PTC-1 activation is an early event in malignant
transformation. If the latter is the case, it may be that, in a defined sub
set of the cell population, ret/PTC-1 activation elicits an autoimmune resp
onse, which, while possibly curtailing the development of PTC in the majori
ty of cases, results in destruction of the thyroid parenchyma.