Expression of the chromatin remodeling factor Rsf-1 is upregulated in ovarian carcinoma effusions and predicts poor survival.
OBJECTIVE
We recently identified Rsf-1, a chromatin remodeling gene, as a potential oncogene that is frequently amplified and overexpressed in ovarian serous carcinoma. However, its clinical role in ovarian cancer effusions is not clear. In the present study, we assessed the clinical significance of Rsf-1 overexpression in ovarian carcinoma effusions.


METHODS
Formalin-fixed paraffin-embedded sections from 168 effusions (134 peritoneal, 34 pleural) were analyzed for Rsf-1 expression using immunocytochemistry. Matched primary tumors (n=48) and solid metastases (n=73) from 48 patients were additionally studied. Rsf-1 expression in tumor cells in effusions was analyzed for possible association with clinicopathologic parameters and survival.


RESULTS
Rsf-1 protein expression was found in carcinoma cells in 157/168 (93%) effusions. Of these, 70 (45%) stained weakly and 87 (55%) strongly. Specimens from patients diagnosed with FIGO stage IV disease had higher staining score (extent x intensity) compared with stage III tumors (P=0.008). Rsf-1 expression level was significantly lower in primary tumors and solid metastases (P<0.001 for extent, intensity and score). Univariate survival analysis for 59 patients with post-chemotherapy recurrence effusions demonstrated a significant association between higher Rsf-1 staining and shorter overall survival (OS; P=0.009 for staining extent and intensity, P=0.02 for staining score). FIGO stage was the only clinical parameter associated with OS in this group (P=0.032). In Cox analysis, Rsf-1 expression (P=0.022 for staining extent and intensity, P=0.045 for staining score) and FIGO stage (P=0.035) were independent predictors of shorter survival.


CONCLUSIONS
Rsf-1 is frequently expressed and upregulated in ovarian carcinoma cells in effusions and is a novel prognostic marker for patients with post-chemotherapy recurrent disease. The above findings support a role of Rsf-1 in mediating disease progression and aggressive clinical behavior in this subset of ovarian carcinoma patients.
Davidson
Ben
B
Department of Pathology, National Hospital-Norwegian Radium Hospital, University of Oslo, Montebello N-0310 Oslo, Norway. ben.davidson@radiumhospitalet.no
Trope'
Claes G
CG
Wang
Tian-Li
TL
Shih
Ie-Ming
IeM
D018262:Adenocarcinoma, Clear Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001202:Ascitic Fluid / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D018282:Cystadenocarcinoma, Mucinous / Q000235:genetics / Q000401:mortality / Q000473:pathology; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000401:mortality / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D009664:Norway; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D016019:Survival Analysis; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D002843:Chromatin