PEA3 Is the Second Ets Family Transcription Factor Involved in Tumor Progression in Ovarian Carcinoma

Purpose: The purpose of this study was to analyze the possible correlation between PEA3 mRNA expression and survival in advanced-stage ovarian carcinomas, studying two patient groups with extremely different disease outcome. Experimental Design: Sections from 61 primary ovarian carcinomas and metastatic lesions from 36 patients diagnosed with advanced-stage ovarian carcinoma [International Federation of Gynecologists and Obstetricians (FIGO) stages III-IV] were evaluated for expression of PEA3 using mRNA in situ hybridization. Patients were divided into long-term ( n = 16) and short-term ( n = 20) survivors. Results: The mean values for disease-free survival and overall survival were 119 and 137 months for long-term survivors, as compared with 4 and 22 months for short-term survivors, respectively. Expression of PEA3 mRNA was detected in carcinoma cells and stromal cells in 56 of 61 lesions (92%) and 54 of 61 lesions (89%), respectively. Intense stromal expression was detected only in the vicinity of grade 2–3 tumors ( P = 0.04). PEA3 expression in stromal cells showed a significant association with matrix metalloproteinase 2 mRNA expression in carcinoma cells ( P = 0.022). PEA3 expression in carcinoma cells showed an association with mRNA expression of the β 1 integrin subunit in the same compartment ( P = 0.039). It was also associated with mRNA expression of β 1 integrin subunit ( P = 0.012), basic fibroblast growth factor ( P = 0.036), and the matrix metalloproteinase inducer EMMPRIN ( P = 0.038) in stromal cells. PEA3 mRNA was detected more often in both carcinoma and stromal cells in tumors of short-term survivors ( P = 0.021 for stromal cells). In univariate survival analysis, PEA3 expression in stromal cells correlated with both shorter disease-free survival ( P = 0.019) and overall survival ( P = 0.029), whereas tumor cell expression predicted poor overall survival ( P = 0.049). PEA3 mRNA expression in stromal cells emerged as an independent predictor of poor outcome in multivariate survival analysis, in which all molecules previously studied in this patient cohort were included ( P = 0.015). Conclusions: To the best of our knowledge, this is the first evidence associating PEA3 mRNA expression and poor survival in human epithelial malignancy. PEA3 is thus a novel prognostic marker in advanced-stage ovarian carcinoma. The association between PEA3 mRNA expression and the expression of the β 1 integrin subunit, basic fibroblast growth factor, and EMM