Comparison of macroscopic appearance and estrogen receptor-alpha regulators after gene alteration in human endometrial cancer

The existence of two types of endometrial cancer (hyperplasia-associated ty pe [type I] and atrophy-associated type [type III) is well established. To test if different molecular genetic pathways are involved in the pathogenes is of type I and II disease, we examined pathologic features and the geneti c alterations of K-Ras, MDM2 and p53 (which are considered to be involved i n regulation of the estrogen receptor-alpha) in human endometrial tissue sa mples using several modified PCR methods. We found a significant difference in histologic grade (P < 0.001), degree of invasion (P < 0.001), stage gro uping (P < 0.001) and estrogen receptor status (P < 0.01) between type I an d II cases. There was a tendency for cases with K-Ras point mutations to be of type I, and for cases with the p53 point mutation to be of type II; how ever, we found that these mutations or alternative splicing of MDM2 was rar ely involved and there was no significant difference in frequency of these alterations between types I and II. There must therefore be another structu ral or functional difference of Ras, MDM2 or p53 between type I and type II cancer. These unknown factors may be responsible for the difference betwee n estrogen-dependent and estrogen-independent growth in human endometrial c ancer.