Ets-1 mRNA expression in effusions of serous ovarian carcinoma patients isa marker of poor outcome

Ets-1 proto-oncogene is a transcription factor with a role in the activatio n of metastasis-associated molecules. We recently found that Ets-1 mRNA exp ression in solid tumors is a marker of poor prognosis in ovarian carcinoma. The objective of this study was to compare the expression of Ets-1 mRNA in effusions and primary and metastatic tumors of serous ovarian carcinoma pa tients and to evaluate its prognostic role in effusions. Sections from 67 m alignant effusions and 90 primary and metastatic lesions were evaluated for expression of Ets-1 using mRNA in situ hybridization. Expression of Ets-1 mRNA was detected in carcinoma cells in 24 of 67 (36%) effusions. Expressio n in cancer cells was similar in peritoneal and pleural effusions. In solid lesions Ets-1 expression was detected in both tumor cells and stromal cell s in 34 of 90 (38%) lesions. Ets-l expression in tumor cells showed a stron g association with that of stromal cells (p <0.001). Ets-1 expression in ef fusions showed an association with mRNA expression of basic fibroblast grow th factor, previously studied in this patient cohort (p = 0.019). Ets-1 exp ression in solid lesions showed an association with mRNA expression of vasc ular endothelial,growth factor (p <0.001 for both carcinoma and stromal cel ls), basic Fibroblast growth factor (p = 0.007 for carcinoma cells, p = 0.0 06 for stromal cells), and interleukin-8 IL-8) (p = 0.001 for tumor cells). Ets-1 mRNA showed upregulation in metastases when compared with effusion s pecimens (p = 0.028). In univariate survival analysis Ets-1 expression in c arcinoma cells in effusions correlated with poor survival (p = 0.003). Our findings confirm the role of Ets-1 as a novel prognostic marker in advanced -stage ovarian carcinoma and extend it to effusion specimens. The elevated expression in solid metastases supports a central role in tumor progression as well, The association between Ets-1 mRNA expression and the expression of angiogenic genes, documented also in our previous study, points to the c lose link between these molecules, in agreement with the role of angiogenic genes in the transcriptional activation of Ets-1. The identical phenotype of carcinoma cells in pleural and peritoneal effusions provides further evi dence for our theory that cells at these sites share similar genotypic and phenotypic profiles.