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

The immunohistochemical expression of p53, p21, Rb, p16. cyclin Dl, Ki67, c yclin A, cyclin Bl, p27, bcl2, bax, and 6ak proteins and the apoptotic inde x (At) were investigated in 20 normal thymuses (8 adults, 3 adolescents, 5 infants and 4 newborns). The expressions of Rb, Ki67, cyclin A and cyclin B I 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 cyclin B1 expression in thymuses were 77.2%, 32.2% and 21.4% (newborns), 62.4%, 33.7% and 18.5% (i nfants), 56.9%, 23.4% and 18.9% (adolescents) and 38.7%, 21.7% and 14.6% (a dults), respectively. The mean values of At in thymuses from newborns, infa nts, adolescents and adults were 1.4%, 2.9%, 2.7% and 3.8%, respectively. T his decrease in proliferation and increase in apoptosis may account for the process of thymic involution. P16 expression was widespread with most of H assall's corpuscles being p16-positive. P16-positive cells and Hassall's co rpuscles increased with the increase in age, in keeping with the suggested role of p16 in cellular senescence. P27 expression was undetectable in subc apsular thymocytes with a tendency for increased expression toward the medu lla. The expressions of Ki67, cyclin A and cyclin B I 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 p5 3 proteins were mainly detected in a part of the subcapsular cortical epith elial cells. These findings suggest that a) in thymocytes, the apoptotic pa thway is mostly p53-independent and the function of p21 as a negative regul ator of the cell cycle 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 p2l expression may be induced by p53, but in most of them seems to be p53-independent. Most of Hassall's corpuscles were p21-positive, consistent with previous evidence that these structures repr esent end stages of maturation of thymic medullary epithelium and that p21 protein is involved in the process of terminal differentiation. Cyclin DI p ositivity was found in some macrophages. Bcl2 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 play a broader role than bcl2 in th e regulation of thymic apoptosis.