Immunohistochemical expression of p53, p21/waf1, Rb, p16, cyclin D1, p27, Ki67, cyclin A, cyclin B1, bcl2, bax and bak proteins and apoptotic index in normal thymus

• Kanavaros, Panagiotis ^[3] ; Stefanaki, K. ^[4] ; Rontogianni, D. ^[5] ; Papalazarou, D. ^[3] ; Sgantzos, M. ^[3] ; Arvanitis, D. ^[3] ; Vamvouka, C. ^[5] ; Gorgoulis, V. ^[1] ; Siatitsas, I. ^[2] ; Agnantis, N.J. ^[6] ; Bai, M. ^[6]
  1. [1] National and Kapodistrian University of Athens

     National and Kapodistrian University of Athens

     Dimos Athens, Grecia

     
  2. [2] University of Crete

     University of Crete

     Dimos Heraklion, Grecia

     
  3. [3] Departments of Histology and Anatomy, University of Thessalia
  4. [4] Department of Pathology, Agia Sophia Childrens' Hospital of Athens
  5. [5] 0epartment of Pathology, Evangelismos Hospital of Athens
  6. [6] Department of Pathology, University of loan nina

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• Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 16, Nº. 4, 2001, págs. 1005-1012
• Idioma: inglés
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  • The immunohistochemical expression of p53, p21, Rb, p16, cyclin D1, Ki67, cyclin A, cyclin Bl, p27, bcl2, bax, and bak proteins and the apoptotic index (AI) were investigated in 20 normal thymuses (8 adults, 3 adolescents, 5 infants and 4 newborns). The expressions of Rb, Ki67, cyelin A and cyelin Bl were overlapping, being high in the cortex with a tendency for decreased expression toward the medulla. Apoptotic cells were mainly detected in the cortex and the corticomedullary junction, rarely being present in Hassall's corpuscles. The mean values of Ki67, cyclin A, and cyelin Bl expression in thymuses were 77.2%, 32.2% and 21.4% (newborns), 62.4%, 33.7% and 18.5% (infants), 56.9%, 23.4% and 18.9% (adolescents) and 38.7%, 21.7% and 14.6% (adults), respectively. The mean values of AI in thymuses from newborns, infants, adolescents and adults were 1.4%, 2.9%, 2 .7% and 3.8%, respectively. This decrease in proliferation and increase in apoptosis may account for the process of thymic involution. P16 expression was widespread with most of Hassall's corpuscles being p16-positive. P16-positive cells and Hassall's corpuscles increased with the increase in age, in keeping with the suggested role of p 16 in cellular senescence. P27 expression was undetectable in subcapsular thymocytes with a tendency for increased expression toward the medulla. The expressions of Ki67, cyclin A and cyelin Bl were inversly related with that of p27, consistent with previous evidence that p27 concentration is reduced when the cell-cycle progresses. P21 and much less frequently p53 proteins were mainly detected in a part of the subcapsular cortical epithelial cells. These findings suggest that a) in thymocytes, the apoptotic pathway is mostly p53-independent and the function of p21 as a negative regulator of the cell cyele must be redundant to other negative regulators, such as p16 and p27 which were abundantly detected in thymocytes and b) in some thymic epithelial cells, the p21 expression may be induced by p53, but in most of them seems to be p53-independent. Most of Hassall's corpuscles were p2I-positive, consistent with previous evidence that these structures represent end stages of maturation of thymic medullary epithelium and that p2I protein is involved in the process of terminal differentiation. Cyelin Dl positivity was found in some macrophages. Bel2 expression was mainly seen in medullary thymocytes, reflecting the surviving thymocytes in this region. The expressions of Bax and bak were more widespread in both the medulla and cortex, suggesting that these proteins playa broader role than bcl2 in the regulation of thymic apoptosis.