INCREASED EXPRESSION OF THE NME1 GENE IS ASSOCIATED WITH METASTASIS IN EPITHELIAL OVARIAN-CANCER

The genetic events involved in the development of metastases of epithe lial ovarian cancer are largely unknown. One gene postulated to play a role in tumour metastasis suppression is NME1 (nm23-HI), and an inver se relationship between NME1 expression and metastatic potential has b een observed for some solid tumours. In this study we have investigate d the levels of mRNA expression of the 2 isoforms of the NME gene, NME 1 and NME2. A maximum of 45 tumour samples from 33 patients were avail able for Northern blot analysis. We observed variable levels of expres sion of NME1 and NME2 mRNA. The average level of NME1, but not NME2, m RNA expression was statistically higher in metastatic biopsies when co mpared with primary tumour biopsies. To examine the possible tumour su ppressor gene role of NME1 in ovarian tumours, 76 patients were invest igated by Southern blot analysis to determine the rate of allelic dele tion. Allele loss at 5 other chromosome 17 loci (D17S5, TP53, NF1, D17 S74, D17S4) was also evaluated for many of these 76 patients. Allele l oss was observed in 22/30 (73%) informative patients at the NME1 locus . We also observed high rates of allele loss at the other loci evaluat ed. No correlations with clinical stage, histological subtype or patie nt survival were observed in either mRNA or DNA analyses. We have esta blished that tumour progression in ovarian cancer is accompanied by ov er-expression of the NMEI gene; however, despite high rates of allele loss at the NMEI locus, the concept that NMEI may be a candidate tumou r suppressor gene in ovarian cancer cannot be confirmed by this study. (C) 1995 Wiley-Liss, Inc.