Expression of apoptosis-related antigens, Fas, bcl-2, and p53, and Mib-1 proliferation index in the hypoplastic thymus of DiGeorge syndrome

• Published in: Pediatric and developmental pathology Vol. 5; no. 5; pp. 465 - 471
• Main Authors: Zhou, Holly, Perkins, Sherrie L, Tripp, Sheryl, Hussong, Jerry W, Coffin, Cheryl M
• Format: Journal Article
• Language: English
• Published: United States 01.09.2002
• Subjects: Apoptosis - immunology; Cell Division; DiGeorge Syndrome - metabolism; DiGeorge Syndrome - pathology; fas Receptor - metabolism; Female; Gestational Age; Humans; Immunoenzyme Techniques; Infant, Newborn; Ki-67 Antigen - metabolism; Male; Organ Size; Proto-Oncogene Proteins c-bcl-2 - metabolism; Retrospective Studies; Thymus Gland - abnormalities; Thymus Gland - metabolism; Tumor Suppressor Protein p53 - metabolism
• ISSN: 1093-5266; 1615-5742
• DOI: 10.1007/s10024-002-2004-7

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.