title: Ets-1 mRNA expression in effusions of serous ovarian carcinoma patients is a marker of poor outcome.
abstract: Ets-1 proto-oncogene is a transcription factor with a role in the activation of metastasis-associated molecules. We recently found that Ets-1 mRNA expression 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 patients and to evaluate its prognostic role in effusions. Sections from 67 malignant 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. Expression in cancer cells was similar in peritoneal and pleural effusions. In solid lesions Ets-1 expression was detected in both tumor cells and stromal cells in 34 of 90 (38%) lesions. Ets-1 expression in tumor cells showed a strong association with that of stromal cells (p <0.001). Ets-1 expression in effusions showed an association with mRNA expression of basic fibroblast growth factor, previously studied in this patient cohort (p = 0.019). Ets-1 expression in solid lesions showed an association with mRNA expression of vascular endothelial growth factor (p <0.001 for both carcinoma and stromal cells), basic fibroblast growth factor (p = 0.007 for carcinoma cells, p = 0.006 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 specimens (p = 0.028). In univariate survival analysis Ets-1 expression in carcinoma 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 close 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 evidence for our theory that cells at these sites share similar genotypic and phenotypic profiles.
authors.affiliation: Department of Pathology, the Norwegian Radium Hospital, Oslo, Norway. bend@ulrik.uio.no
authors.forename: B
authors.initials: B
authors.lastname: Davidson
authors.forename: B
authors.initials: B
authors.lastname: Risberg
authors.forename: I
authors.initials: I
authors.lastname: Goldberg
authors.forename: J M
authors.initials: JM
authors.lastname: Nesland
authors.forename: A
authors.initials: A
authors.lastname: Berner
authors.forename: C G
authors.initials: CG
authors.lastname: Tropé
authors.forename: G B
authors.initials: GB
authors.lastname: Kristensen
authors.forename: M
authors.initials: M
authors.lastname: Bryne
authors.forename: R
authors.initials: R
authors.lastname: Reich
mesh_terms: D000328:Adult; D000368:Aged; D001202:Ascitic Fluid / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D015345:Oligonucleotide Probes / Q000737:chemistry; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger / Q000096:biosynthesis*; D012334:RNA, Neoplasm / Q000032:analysis; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D014408:Biomarkers, Tumor; C494041:ETS1 protein, human; D016228:Endothelial Growth Factors; D016209:Interleukin-8; D008222:Lymphokines; C000715470:MAS1 protein, human; D015345:Oligonucleotide Probes; D000090063:Proto-Oncogene Mas; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D019716:Tissue Inhibitor of Metalloproteinase-2; D020782:Matrix Metalloproteinases