Specific expression of hepatocyte nuclear factor-1β in the ovarian clear cell adenocarcinoma and its application to cytological diagnosis

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-1β (HNF-1β) is expressed specifically in clear cell adenocarcinoma (CCC). Thus, in the present study, we investigated the usefulness of HNF-1β as an immunocytochemical diagnostic marker of CCC in ascitic specimens. We first confirmed that HNF-1β 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-1β antibody (P < 0.05). The sensitivity and specificity were calculated to be 0.955 and 0.921, respectively. Immmunostaining patterns of HNF-1β on cytological specimens were similar to those observed on histopathological ovarian specimens from the same patients. Double immunohistochemical staining using anti-HNF-1β antibody and HBME-1, a mesothelium-specific monoclonal antibody, confirmed that anti-HNF-1β antibody distinguished CCC cells and mesothelial cells. In conclusion, our findings indicate the specific expression of HNF-1β in ovarian CCC and possible clinical applications of HNF-1β 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.