Expression and clinical role of the bric-a-brac tramtrack broad complex/poxvirus and zinc protein NAC-1 in ovarian carcinoma effusions.
We recently identified NAC-1, member of the bric-a-brac tramtrack broad complex/poxvirus and zinc domain family, as an overexpressed gene in ovarian serous carcinoma and found more frequent NAC-1 protein expression in recurrent compared to primary tumors. In the present study, we assessed the clinical significance of NAC-1 expression in ovarian carcinoma effusions. Formalin-fixed, paraffin-embedded sections from 176 effusions (137 peritoneal, 39 pleural) and 197 corresponding solid tumors (69 primary tumors, 128 solid metastases) were analyzed for NAC-1 expression using immunohistochemistry. Staining intensity and extent results were analyzed for possible association with clinicopathologic parameters and survival. Nuclear NAC-1 immunoreactivity was found in carcinoma cells in 98% of (173/176) effusions, 94% (65/69) of primary tumors, and 95% (121/128) of metastases. Staining intensity and extent were significantly higher in effusions compared with matched solid tumors (P = .002 for intensity, P = .003 for extent compared with primary tumors; P < .001 for both intensity and extent compared with metastases). Furthermore, NAC-1 expression intensity was significantly higher in specimens obtained after the administration of chemotherapy (P = .002) and correlated with shorter progression-free survival (PFS) in analysis of 62 patients with post-chemotherapy effusions (P = .039). International Federation of Gynecology and Obstetrics stage (IV versus III) was the only clinical parameter associated with PFS in this group (P = .004). In Cox analysis, only the International Federation of Gynecology and Obstetrics stage was an independent predictor of shorter PFS (P = .009). In conclusion, NAC-1 expression is higher in ovarian carcinoma cells in effusions compared with their solid tumor counterparts. NAC-1 is up-regulated in tumor cells after chemotherapy, suggesting a role for this protein in tumor progression and in the development of chemotherapy resistance in ovarian cancer.
Davidson
Ben
B
Pathology Clinic, Rikshospitalet-Radiumhospitalet Medical Center, University of Oslo, N-0310 Montebello Oslo, Norway. Electronic address: ben.davidson@radiumhospitalet.no.
Berner
Aasmund
A
Pathology Clinic, Rikshospitalet-Radiumhospitalet Medical Center, University of Oslo, N-0310 Montebello Oslo, Norway.
Trope'
Claes G
CG
Department of Gynecologic Oncology, Rikshospitalet-Radiumhospitalet Medical Center, University of Oslo, N-0310 Montebello Oslo, Norway.
Wang
Tian-Li
TL
Department of Pathology Johns Hopkins University Medical Institutions, Baltimore, MD 21231, USA; Department of Gynecology, Johns Hopkins University Medical Institutions, Baltimore, MD 21231, USA; Department of Oncology, Johns Hopkins University Medical Institutions, Baltimore, MD 21231, USA.
Shih
Ie-Ming
IM
Department of Pathology Johns Hopkins University Medical Institutions, Baltimore, MD 21231, USA; Department of Gynecology, Johns Hopkins University Medical Institutions, Baltimore, MD 21231, USA; Department of Oncology, Johns Hopkins University Medical Institutions, Baltimore, MD 21231, USA.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001202:Ascitic Fluid / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000032:analysis; D005260:Female; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism*; D016066:Pleural Effusion, Malignant / Q000737:chemistry*; D012097:Repressor Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000032:analysis; D016335:Zinc Fingers
C429757:BTBD1 protein, human; D004268:DNA-Binding Proteins; C516477:NACC1 protein, human; D009363:Neoplasm Proteins; D012097:Repressor Proteins; D014157:Transcription Factors