C-Fos expression is a molecular predictor of progression and survival in epithelial ovarian carcinoma - PubMed (original) (raw)

C-Fos expression is a molecular predictor of progression and survival in epithelial ovarian carcinoma

S Mahner et al. Br J Cancer. 2008.

Abstract

Members of the Fos protein family dimerise with Jun proteins to form the AP-1 transcription factor complex. They have a central function in proliferation and differentiation of normal tissue as well as in oncogenic transformation and tumour progression. We analysed the expression of c-Fos, FosB, Fra-1 and Fra-2 to investigate the function of Fos transcription factors in ovarian cancer. A total of 101 patients were included in the study. Expression of Fos proteins was determined by western blot analysis, quantified by densitometry and verified by immunohistochemistry. Reduced c-Fos expression was independently associated with unfavourable 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 for low, moderate and high c-Fos levels; P=0.003). No correlations were observed for FosB, Fra-1 and Fra-2. We conclude that loss of c-Fos expression is associated with tumour progression in ovarian carcinoma and 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 supported by the recently discovered tumour-suppressing and proapoptotic function of c-Fos in various cancer types.

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Figures

Figure 1

Figure 1

Representative results of c-Fos, FosB, Fra-1 and Fra-2 expression in ovarian carcinomas. As control, protein extracts from the ovarian cancer cell lines Ovcar5 and Ovcar8 as well as the mammary carcinoma cell line MCF7 were included in each gel. Tumour samples were coded as Txxxx and equal amounts of protein (20 _μ_g) were loaded on the gel.

Figure 2

Figure 2

C-Fos immunohistochemistry. (A) Moderately differentiated serous carcinoma with nuclear immunoreactivity in tumour cells (T) and weak immunostaining in nuclei of some stromal fibroblasts (S). 400 × . (B) Poorly differentiated serous carcinoma with only weak c-Fos immunostaining in tumour cells (T) and some fibroblasts (S). 400 × .

Figure 3

Figure 3

C-Fos expression is correlated with progression-free and overall survival (_P_=0.003). Kaplan–Meier curves were generated from 99 patients whose outcome was followed over a median period of 20 months. Patients were stratified based on low, moderate and high c-Fos expression. X axis: survival probability; Y axis: survival (months). Censored cases are indicated by vertical bars.

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