TP53 alterations in relation to the cell cycle-associated proteins p21, cyclin D1, cdk4, RB, MDM2, and EGFR in cancers of the uterine corpus

In the present study, TP53 alterations have been analysed and compared with the expression of the proteins p21, cyclin D1, cdk4, RE, EGFR, and MDM2 in 53 cancers of the uterine corpus, TP53 gene mutation's analysed by CDGE/DG GE and direct sequencing showed a TP53 gene mutation in: 18 per rent of the cases. TP53 gene mutations were not significantly related to overexpressio n or down-regulation of any of the proteins, Immunohistochemically, there w as an increased protein level of TP53 in 77 per cent, p21 in 36 per cent, c yclin D1 in 45 per cent, cdk4 in 77 pet cent, EGFR-in 8 per cent, and MDM2 in 32 per cent of the cases. Expression of RE protein was normal in all can cers. Significant association of protein expression was seen between TP53 a nd MDM2 (p=0.005) and p21 and MDM2 (p=0.001). Furthermore, there may be an association between TP53 and p21 (p=0.038) and cyclin D1 and cdk4 (p=0.045) . The results revealed increased levels of TP53 protein in all MDM2-positiv e cases that did not show TP53 mutations, indicating TP53 protein stabiliza tion and inactivation by complex formation with MDM2 In summary, the high n umber of cases showing an increased level of TP53 and cdk4 proteins suggest s that these proteins play an important role in the neoplastic process in c ancers of the uterine corpus. Copyright (C) 1999 John Wiley & Sons, Ltd.