Specific expression of hepatocyte nuclear factor-1β in the ovarian clear cell adenocarcinoma and its application to cytological diagnosis
Specific expression of hepatocyte nuclear factor-1β in the ovarian clear cell adenocarcinoma and its application to cytological diagnosis
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DOI：
10.1111/j.1349-7006.2007.00398.x
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发表时间：
2007-03-01
期刊：
影响因子：
5.7
通讯作者：
Sakamoto, Michiie
中科院分区：
文献类型：
--
作者：
Higashiguchi, Atsushi;Yamada, Taketo;Sakamoto, Michiie
腹水细胞学诊断是至关重要的，但卵巢腺癌细胞和反应性间皮细胞可能难以区分，因为它们通常具有非典型的细胞核和增加的核/质比。先前使用DNA微阵列的研究已经证明肝细胞核因子-1 β（HNF-1 β）在透明细胞腺癌（CCC）中特异性表达。因此，在本研究中，我们研究了HNF-1 β作为腹水标本CCC免疫细胞化学诊断标志物的有用性。我们首先通过实时荧光定量PCR和免疫组化证实了55例手术标本中CCC中HNF-1 β的表达水平在mRNA（P < 0.05）和蛋白（P <0.05）水平上均显著高于非CCC（即浆液性腺癌、粘液性腺癌和类囊腺癌）。60例CCC细胞免疫组化显示CCC阳性，而非CCC细胞除3例类囊腺癌外，其余均为阴性（P <0.05），背景中的间皮细胞也为阴性（P < 0.05）。敏感性和特异性分别为0.955和0.921。HNF-1 β在细胞学标本上的免疫染色模式与在同一患者的组织病理学卵巢标本上观察到的相似。使用抗HNF-1 β抗体和间皮特异性单克隆抗体HBME-1的双重免疫组织化学染色证实，抗HNF-1 β抗体区分CCC细胞和间皮细胞。总之，我们的研究结果表明，HNF-1 β在卵巢CCC的特异性表达和可能的临床应用HNF-1 β免疫细胞化学染色的差异CCC从非CCC的细胞病理学诊断，以及从间皮瘤细胞从卵巢癌患者的细胞学标本。
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-1 beta (HNF-1 beta) is expressed specifically in clear cell adenocarcinoma (CCC). Thus, in the present study, we investigated the usefulness of HNF-1 beta as an immunocytochemical diagnostic marker of CCC in ascitic specimens. We first confirmed that HNF-1 beta 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-1 beta antibody (P < 0.05). The sensitivity and specificity were calculated to be 0.955 and 0.921, respectively. Immmunostaining patterns of HNF-1 beta on cytological specimens were similar to those observed on histopathological ovarian specimens from the same patients. Double immunohistochemical staining using anti-HNF-1 beta antibody and HBME-1, a mesothelium-specific monoclonal antibody, confirmed that anti-HNF-1 beta antibody distinguished CCC cells and mesothelial cells. In conclusion, our findings indicate the specific expression of HNF-1 beta in ovarian CCC and possible clinical applications of HNF-1 beta 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.