Graves-Basedow disease goiter: a model of Bax-Bcl2 regulated apoptosis.
This study demonstrates the involvement of a Bax-Bcl2-dependent apoptotic process in Graves-Basedow thyroid disease, a pathological condition known for its spontaneously oscillating evolution. A continuous series of 86 cases of surgically treated Graves' thyroid was evaluated for apoptotic cell content identified by histological criteria and confirmed by terminal desoxynucleotidyl transferase-mediated desoxyuridine triphosphate nick end-labeling (TUNEL). A significant correlation was found between tissue features of Graves' disease (epithelial hyperplasia, cellular hypertrophy, colloid content) and the amount of apoptotic cells. No correlation was found with lymphocytic infiltrates. Significantly, 11 cases (about 12% of the series) with high-level apoptosis displayed the typical features of active Graves' disease over all tissue sections. In contrast, cases with no detectable apoptosis exhibited regressive tissue features of Graves' disease. An intermediate group of cases was characterized by tissue heterogeneity with hyperactive foci, rich in apoptosis, alternating with regressive areas lacking apoptosis. In this group the participation of apoptosis to the remodeling of Graves' thyroid parenchyma, in a tight balance with cell proliferation, was best illustrated. Moreover, the thyroid follicle by accumulating apoptotic cells and bodies, allowed a tentative chronological ordering of apoptosis steps in correlation with Bax-Bcl2 tissue distribution and cellular pattern. Our observations suggest that the initiation of apoptosis corresponds to a loss of cellular cohesion, a drop in Bcl2 expression, and a delocalization of Bax from a putative Golgi storage location to a mitochondrial distribution.
Labat-Moleur
F
F
Laboratoire de Pathologie Cellulaire, Centre Hospitalier Universitaire, Grenoble, France. Elisabeth.Brambilla@ujf-grenoble.fr
Chabre
O
O
Guillermet
C
C
Chaffanjon
P
P
Blumet-Rondeu
F
F
Bauchet
A
A
Franc
B
B
Brambilla
E
E
Bachelot
I
I
Dumont
J E
JE
Negoescu
A
A
D000328:Adult; D017209:Apoptosis; D003102:Colloids / Q000032:analysis; D006111:Graves Disease / Q000145:classification / Q000473:pathology* / Q000601:surgery; D006801:Humans; D006965:Hyperplasia; D006984:Hypertrophy; D020287:In Situ Nick-End Labeling; D008214:Lymphocytes / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D013961:Thyroid Gland / Q000473:pathology*; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D003102:Colloids; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein