C-Fos Expression as Predictor of Progression and Survival in Epithelial Ovarian Carcinoma

Background

Members of the Fos protein family dimerize with Jun proteins to form the AP–1 transcription factor complex. They play a central role in proliferation and differentiation of normal tissue as well as in oncogenic transformation and tumor progression. To investigate the role of Fos transcription factors in ovarian cancer, we analyzed the expression of c-Fos, FosB, Fra–1 and Fra–2 in patients with invasive epithelial ovarian carcinoma.

Materials and Methods

A total of 101 ovarian cancer patients who presented for initial surgery were included in the study. Protein expression was determined by Western Blot analysis and quantified by densitometry. Correlation between Fos protein expression and clinicopathologic factors (age, FIGO-stage, histology, grade, nodal involvement, CA–125) as well as progression-free survival and overall survival was examined.

Results

Reduced c-Fos expression was independently associated with reduced progression-free survival (20.6, 31.6 and 51.2 months for patients with low, moderate and high c-Fos expression; p=0.003) as well as overall survival (23.8, 46.0 and 55.5 months ; p=0.003). In addition, an inverse correlation with tumor grade (p=0.038) was noticed. No correlations were observed for FosB, Fra–1, Fra–2 and the other clinicopathologic factors evaluated.

Conclusions

Our study demonstrates for the first time, that loss of c-Fos expression correlates with tumor progression in ovarian carcinoma and suggests that c-Fos may be a prognostic factor. These results are in contrast to the classic concept of c-Fos as an oncogene, but are well supported by the recently discovered tumor-suppressing and pro-apoptotic function of c-Fos in various cancer types.

ovarian cancer - prognostic factors - c-Fos - AP-1