Z. Jiang et al., Frequency and distribution of DNA fragmentation in Hashimoto's thyroiditisand development of papillary thyroid carcinoma, ENDOCR PATH, 10(2), 1999, pp. 137-144
Downregulation of apoptosis and high expression of bcl-2 play an important
role in the development of follicular lymphoma. However, little is known ab
out apoptosis in thyroid disease, particularly with respect to the developm
ent of papillary carcinoma from Hashimoto's thyroiditis. To study the early
stages of cell death in various types of thyroid disease, surgical specime
ns from 31 patients including Hashimoto's thyroiditis (HT, n = 7), papillar
y carcinoma (PC, n = 2), Hashimoto's thyroiditis with papillary carcinoma (
HTPC, n = 5), and Graves' disease (GD, n = 7) were examined by an in situ n
ucleotidyl transferase assay (ISNTA), which detects DNA fragmentation. Cont
rol normal thyroid tissue (NT, n = 7) was obtained from surgically resected
papillary thyroid carcinomas sampled away from the primary tumor. An immun
ohistochemical (IHC) method was used to detect bcl-2 expression. Positive I
SNTA nuclei in thyroid follicular cells or tumor cells per section were cou
nted in all parenchymal areas, excluding areas of lymphocyte aggregates. Th
e intensity of bcl-2 staining was graded on a scale of 1+ to 3+. The number
of ISNTA-positive thyroid follicular cells was a significantly higher in H
T compared to GD. In addition, there was significantly lower number of ISNT
A positive non-neoplastic thyroid follicular cells in HTPC compared to HT a
lone. Strong expression of bcl-2 was found in all cases of GD and NT, but m
uch less bcl-2 staining was seen in HT There was moderate expression of bcl
-2 in HTPC and PC. These findings suggest that (1) DNA fragmentation of the
thyroid follicular cells plays an important role in the thyroid injury in
HT but not in GD, (2) expression of bcl-2 may overcome the apoptosis in GD
but not in HT, and (3) downregulation of DNA fragmentation of the follicula
r cells in Hashimoto's thyroiditis associated with papillary carcinoma may
suggest an important mechanism for tumor pathogenesis.