EXPRESSION OF THE ZINC-FINGER GENE EVI-1 IN OVARIAN AND OTHER CANCERS

The EVI-1 gene was originally detected as an ectopic viral insertion s ite and encodes a nuclear zinc finger DNA-binding protein. Previous st udies showed restricted EVI-1 RNA or protein expression during ontogen y; in a kidney and an edometrial carcinoma cell line; and in normal mu rine oocytes and kidney cells. EVI-1 expression was also detected in a subset of acute myeloid leukaemias (AMLs) and myelodysplasia. Because EVI-1 is expressed in the urogenital tract during development, we exa mined ovarian cancers and normal ovaries for EVI-1 RNA expression usin g reverse transcription-polymerase chain reaction (RT-PCR) and RNAase protection. Chromosome abnormalities were examined using karyotypes an d whole chromosome 3 and 3q26 fluorescence in situ hybridisation (FISH ). RNA from six primary ovarian tumours, five normal ovaries and 47 tu mour cell lines (25 ovarian, seven melanoma, three prostate, seven bre ast and one each of bladder, endometrial, lung epidermoid and histiocy tic lymphoma) was studied. Five of six primary ovarian tumours, three of five normal ovaries and 22 of 25 ovarian cell lines expressed EVI-1 RNA. A variety of other non-haematological cancers also expressed EVI -1 RNA. Immunostaining of ovarian cancer cell lines revealed nuclear E VI-1 protein. In contrast, normal ovary stained primarily within oocyt es and faintly in stroma. Primary ovarian tumours showed nuclear and i ntense, diffuse cytoplasmic staining. Quantitation of EVI-1 RNA, perfo rmed using RNAase protection, showed ovarian carcinoma cells expressed 0 to 40 times the EVI-1 RNA in normal ovary, and 0-6 times the levels in leukaemia cell lines. Southern analyses of ovarian carcinoma cell lines showed no amplification or rearrangements involving EVI-1. In so me acute leukaemias, activation of EVI-1 transcription is associated w ith translocations involving 3q26, the site of the EVI-1 gene. Ovarian carcinoma karyotypes showed one line with quadruplication 3(q24q27), but no other clonal structural rearrangements involving 3q26. However, whole chromsome 3 and 3q26 FISH performed on lines with high EVI-1 ex pression showed translocations involving chromosome 3q26. EVI-1 is ove rexpressed in ovarian cancer compared with normal ovaries, suggesting a role for EVI-1 in solid tumour carcinogenesis or progression. Mechan isms underlying EVI-1 overexpression remain unclear, but may include r earrangements involving chromosome 3q26.