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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.
AuthorsAtsushi Higashiguchi, Taketo Yamada, Nobuyuki Susumu, Taisuke Mori, Atsushi Suzuki, Daisuke Aoki, Michiie Sakamoto
JournalCancer science (Cancer Sci) Vol. 98 Issue 3 Pg. 387-91 (Mar 2007) ISSN: 1347-9032 [Print] England
PMID17270029 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Biomarkers, Tumor
  • Hepatocyte Nuclear Factor 1-beta
Topics
  • Adenocarcinoma, Clear Cell (diagnosis, genetics, metabolism, pathology)
  • Biomarkers, Tumor (genetics, metabolism)
  • Cell Line, Tumor
  • Diagnosis, Differential
  • Female
  • Hepatocyte Nuclear Factor 1-beta (metabolism)
  • Humans
  • Immunohistochemistry
  • Ovarian Neoplasms (diagnosis, genetics, metabolism, pathology)
  • Retrospective Studies
  • Sensitivity and Specificity

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