Endometrial carcinoma is the most common gynaecologic malignancy in industrialized countries. Mechanisms involved in endometrial carcinogenesis are not fully understood and the classic prognostic factors failed in some cases to predict clinical outcome. In the current study, we analysed the expression of metalloproteinases (MMP-2,- 7 and -9) and tissue inhibitors of metalloproteinases (TIMP-1 and -2) in normal endometrium, endometrial hyperplasia and endometrial cancer. Our results support the involvement of MMPs and TIMPs in endometrial carcinogenesis. Strong MMP-2 and weak TIMP-2 expression were potent markers of endometrial aggressiveness with a high risk of local and distant spread. TP53 loss of heterozygosity (LOH) was preferentially detected in serous endometrial carcinomas and in high-grade endometrioid carcinomas suggesting that different pathways may be involved in endometrial carcinogenesis. In endometrial cancer, TP53 FISH does not appear to add significant prognostic data compared with routine immunohistochemistry. Finally, histopronostic correlations established in this work suggest that concomitant evaluation of the expression of MMP-2, TIMP-2, ploidy, p53, Ki67 and oestrogen and progesterone receptors on specimens could select patients at high risk of local recurrence and distant spread.
