Expression of apoptosis-related antigens, Fas, bcl-2, and p53, and Mib-1 proliferation index in the hypoplastic thymus of DiGeorge syndrome.
Apoptosis, along with cellular proliferation, plays a major role in normal developmental processes and tissue homeostasis. We hypothesized that altered apoptosis-related pathways and/or reduced cell proliferation might play a role in the thymic hypoplasia or aplasia in DiGeorge syndrome (DG). We used immunohistochemistry to evaluate the apoptosis-related antigens Fas (CD95), bcl-2, and p53, as well as Mib-1 proliferation index in the thymuses from six patients with DG. The results were compared with those from the thymuses from six patients with non-DG congenital heart disease. All DG patients (age 32 weeks GA to 4 months) had hypoplastic thymuses ranging from microscopic foci to 2.7 g in weight (expected for age, 4.7 +/- 3.6 g to 10 +/- 6 g). The thymic weights from the patients with non-DG congenital heart disease (age 37 weeks GA to 1 month) ranged from 3 to 5.6 g and were at the lower range of expected weight by age (expected for age, 8.4 +/- 5.6 g to 12 +/- 7 g). All thymuses showed histologic features of stress-induced involution. In both groups, a - 50% Mib-1 proliferation index was found in the cortical thymocytes, whereas <5% Mib-1 labeling was seen in the medullary thymocytes; Fas stained medullary epithelial cells (3+) and cortical epithelial cells (1+); bcl-2 stained medullary thymocytes (3+) and cortical thymocytes (1+); p53 stained less than 1% of nuclei in all sections. No significantly altered Mib-1 proliferation index or expression of Fas, bcl-2, and p53 was observed in the hypoplastic thymuses in DG, compared to these same measures in non-DG. These results suggest that thymic hypoplasia in DG may be mediated by mechanisms other than reduced cellular proliferation and/or altered Fas, bcl-2, and p53 apoptotic pathways.
Department of Pathology, University of Utah, School of Medicine, 50 North Medical Drive, Salt Lake City, UT 84132, USA. pchzhou@ihc.com
Holly
H
Zhou
Sherrie L
SL
Perkins
Sheryl
S
Tripp
Jerry W
JW
Hussong
Cheryl M
CM
Coffin
D017209:Apoptosis / Q000276:immunology*; D002455:Cell Division; D004062:DiGeorge Syndrome / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005865:Gestational Age; D006801:Humans; D007124:Immunoenzyme Techniques; D007231:Infant, Newborn; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D009929:Organ Size; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012189:Retrospective Studies; D013950:Thymus Gland / Q000002:abnormalities / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism*
D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor