title: Specific expression of hepatocyte nuclear factor-1beta in the ovarian clear cell adenocarcinoma and its application to cytological diagnosis.
abstract: Ascitic cytological diagnosis is critical, but ovarian adenocarcinoma cells and reactive mesothelial cells can be difficult to distinguish because they usually have atypical cell nuclei and increased nuclear/cytoplasmic ratios. Previous studies using DNA microarrays have demonstrated that hepatocyte nuclear factor-1beta (HNF-1beta) is expressed specifically in clear cell adenocarcinoma (CCC). Thus, in the present study, we investigated the usefulness of HNF-1beta as an immunocytochemical diagnostic marker of CCC in ascitic specimens. We first confirmed that HNF-1beta expression levels were significantly higher in CCC than in non-CCC (i.e. serous adenocarcinoma, mucinous adenocarcinoma and endometrioid adenocarcinoma) in 55 surgical specimens at both the mRNA (P < 0.05) and protein (P < 0.05) levels by real-time polymerase chain reaction and immunohistochemistry, respectively. Immunocytochemistry of 60 cytological specimens showed significant positivity in CCC cases whereas all non-CCC cells, except for three endometrioid adenocaricnoma cases, and mesothelial cells in the background stained negatively for anti-HNF-1beta antibody (P < 0.05). The sensitivity and specificity were calculated to be 0.955 and 0.921, respectively. Immmunostaining patterns of HNF-1beta on cytological specimens were similar to those observed on histopathological ovarian specimens from the same patients. Double immunohistochemical staining using anti-HNF-1beta antibody and HBME-1, a mesothelium-specific monoclonal antibody, confirmed that anti-HNF-1beta antibody distinguished CCC cells and mesothelial cells. In conclusion, our findings indicate the specific expression of HNF-1beta in ovarian CCC and possible clinical applications of HNF-1beta immunocytochemical staining for the differential cytopathological diagnosis of CCC from non-CCC, as well as from mesothelial cells using cytological specimens from ovarian carcinoma patients.
authors.affiliation: Department of Pathology, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Higashiguchi
authors.forename: Taketo
authors.initials: T
authors.lastname: Yamada
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Susumu
authors.forename: Taisuke
authors.initials: T
authors.lastname: Mori
authors.forename: Atsushi
authors.initials: A
authors.lastname: Suzuki
authors.forename: Daisuke
authors.initials: D
authors.lastname: Aoki
authors.forename: Michiie
authors.initials: M
authors.lastname: Sakamoto
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D003937:Diagnosis, Differential; D005260:Female; D051539:Hepatocyte Nuclear Factor 1-beta / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D051539:Hepatocyte Nuclear Factor 1-beta