Expression of hepatocyte nuclear factor-1beta (HNF-1beta) in clear cell tumors and endometriosis of the ovary
Expression of hepatocyte nuclear factor-1beta (HNF-1beta) in clear cell tumors and endometriosis of the ovary
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DOI：
10.1038/modpathol.3800492
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发表时间：
2006-01-01
期刊：
影响因子：
7.5
通讯作者：
Motoyama, T
中科院分区：
文献类型：
--
作者：
Kato, N;Sasou, S;Motoyama, T
卵巢透明细胞瘤常与卵巢子宫内膜异位症有关。在临床病理学上，已经提出透明细胞肿瘤是由子宫内膜异位症发展而来的，但很少有分子证据支持这一推测。最近的微阵列分析显示，肝细胞核因子-1 β（HNF-1 β）在卵巢透明细胞癌中显著上调。在本研究中，我们检查了30例透明细胞肿瘤（26例恶性，3例交界性和1例良性）和40例增生性囊肿，以澄清卵巢子宫内膜异位症是否已经开始分化为透明细胞谱系。所有30例透明细胞肿瘤，包括交界性和良性透明细胞肿瘤，HNF-1 β均在细胞核内表达，而其他类型的卵巢上皮性肿瘤（浆液性、黏液性和Brenner肿瘤）很少表达。在30例透明细胞肿瘤中，17例（56%）与子宫内膜异位症有关，12例可见增生上皮。在12例中的9例中，HNF-1 β的核免疫染色在上皮细胞增生和透明细胞瘤中检测到。在不典型子宫内膜异位症（4例）或反应性子宫内膜异位症（5例）中观察到HNF-1 β表达。此外，40例无肿瘤的增生性囊肿中有16例（40%）也表达HNF-1 β，并且几乎仅在显示炎性囊肿的上皮中观察到表达。我们的研究结果表明HNF-1 β是卵巢透明细胞肿瘤（包括良性、交界性和恶性病变）的一个极好的分子标志物。卵巢子宫内膜异位症不仅在不典型的子宫内膜异位症中，而且在具有退行性和再生性改变的子宫内膜异位症中，早期分化为透明细胞谱系，这可能是卵巢子宫内膜异位症中透明细胞癌频繁发生的原因。
Clear cell tumors of the ovary are frequently associated with ovarian endometriosis. Clinicopathologically, it has been suggested that clear cell tumors develop from endometriosis, but there has been little molecular evidence supporting this speculation. Microarray analysis revealed recently that hepatocyte nuclear factor-1beta (HNF-1beta) was significantly upregulated in clear cell carcinoma of the ovary. In the present study, we examined 30 clear cell tumors ( 26 malignant, three borderline, and one benign) and 40 endometriotic cysts to clarify if differentiation into the clear cell lineage already begins in ovarian endometriosis. All of the 30 clear cell tumors, including borderline and benign ones, showed immunohistochemical expression of HNF-1beta in the nucleus, while other types of ovarian epithelial tumors (endometrioid, serous, mucinous, and Brenner tumors) rarely expressed it. Among 30 clear cell tumors, 17 (56%) cases were associated with endometriosis, and endometriotic epithelium was identified in 12 cases. In nine of the 12 cases, distinct nuclear immunostaining for HNF-1beta was detected in the endometriotic epithelium, as well as in the clear cell tumor. HNF-1beta expression was observed either in atypical endometriosis ( four cases), or in endometriosis of a reactive nature ( five cases). Furthermore, 16 of 40 (40%) endometriotic cysts without a neoplasm also expressed HNF-1beta, and the expression was almost exclusively observed in the epithelium showing inflammatory atypia. Our results indicate that HNF-1beta is an excellent molecular marker for ovarian clear cell tumors, including benign, borderline and malignant lesions. Early differentiation into the clear cell lineage takes place in ovarian endometriosis, not only in atypical endometriosis, but also in endometriosis with degenerative and regenerative changes, and this is probably responsible for the frequent occurrence of clear cell carcinoma in ovarian endometriosis.