Ets-1 messenger RNA expression is a novel marker of poor survival in ovarian carcinoma

Ets-1 proto-oncogene is a transcription factor involved in several cellular functions, including the activation of several proteases participating in tumor invasion and metastasis, The objective of this study was to analyze t he possible correlation between Ets-1 mRNA expression and survival in advan ced-stage ovarian carcinomas, studying two patient groups with extremely di fferent disease outcome. Sections from 66 primary ovarian carcinomas and me tastatic lesions from 41 patients diagnosed with advanced-stage ovarian car cinoma (International Federation of Gynecologists and Obstetricians stages III and IV) were evaluated for expression of Ets-1 using mRNA in situ hybri dization, Patients were divided into long-term (n = 17) and short-term (n = 24) survivors. The mean values for disease-free survival and overall survi val were 116 and 133 months for long-term survivors, as compared to 3 and 2 1 months for short-term survivors, respectively, Expression of Ets-1 mRNA w as detected in carcinoma cells and stromal cells in 28 of 66 (42%) and 22 o f 66 (33%) lesions, respectively, Ets-1 expression showed an association wi th mRNA expression of vascular endothelial growth factor (P = 0.001 for car cinoma cells; P = 0.004 for stromal cells), basic fibroblast growth factor (P = 0.049 for carcinoma cells), and membrane type-1 matrix metalloproteina se (P = 0.045), which were previously studied in this patient cohort. Ets-1 mRNA was detected more often in both carcinoma and stromal cells in tumors of short-term survivors (P = 0.038 for carcinoma cells). In univariate sur vival analysis for all cases, Ets-1 expression in both tumor (P = 0.018) an d stroma (P = 0.026) correlated with poor survival, These findings were rep roduced in an analysis of primary tumors alone (P = 0.039 for tumor cells; P < 0.001 for stromal cells). Ets-1 mRNA expression in stromal cells retain ed its predictive power in a multivariate survival analysis in which all mo lecules studied previously in this patient cohort were included (P = 0.007) , To our knowledge, this is the first evidence associating Ets-1 mRNA expre ssion and poor survival in human epithelial malignancy. Ets-1 is thus a nov el prognostic marker in advanced-stage ovarian carcinoma. The association b etween Ets-1 mRNA expression and the expression of membrane type-1 matrix m etalloproteinase and angiogenic genes, first documented here in a study of patient material, points to the central role of this transcription factor i n tumor progression in ovarian carcinoma.