Okamoto Sanshiro, Okamoto Aikou, Nikaido Takashi, Saito Misato, Takao Miho, Yanaihara Nozomu, Takakura Satoshi, Ochiai Kazunori, Tanaka Tadao
Department of Obstetrics and Gynecology, Jikei University School of Medicine, Tokyo 105-8461, Japan.
Oncol Rep. 2009 May;21(5):1209-14. doi: 10.3892/or_00000343.
Most ovarian cancers arise from the mesothelial surface lining of the ovaries or from invaginations of this lining into the superficial ovarian cortex that form cortical inclusion cysts. Thus, these cysts are thought to be precursor lesions of ovarian carcinoma. Epithelial-mesenchymal transition, which is a transcriptional program for inducing maintenance of the mesenchymal phenotype, acts in tumor progression and metastasis. Little is known about the mechanisms involved in mesenchymal-epithelial transition (MET). We aimed to characterize the human ovarian surface epithelium (OSE) and inclusion cysts by immunohistochemical analysis to examine whether MET occurs during inclusion cyst formation in the OSE. We used specimens from 9 endometrial cancer patients who had undergone hysterectomy and bilateral salpingo-oophorectomy. Immunohistochemical analysis was performed in 10 normal ovaries containing 92 inclusion cysts and in 4 normal tubes to examine the expression of antigen markers including calretinin, podoplanin, D2-40, thrombomodulin, HBME-1, vimentin, EMA, WT1, CA125, MOC31, TAG-72, Ber-EP4 and E-cadherin. The positive staining rates for mesothelial markers in normal OSE were 100% (10/10) for calretinin, 80% (8/10) for podoplanin, 80% (8/10) for D2-40, 70% (7/10) for thrombomodulin, 100% (10/10) for HBME-1, 100% (10/10) for vimentin. The positive staining rates for epithelial markers in tubal epithelium were 100% (4/4) for HBME-1, 100% (4/4) for vimentin, 100% (4/4) for EMA, 75% (3/4) for TAG-72, 100% (4/4) for Ber-EP4. Inclusion cysts showed positive staining for both markers with an incidence of 51% (47/92) for HBME-1, 44% (41/92) for vimentin, 65% (60/92) for TAG-72, 88% (81/92) for Ber-EP4. The OSE showed the characteristics of both mesenchymal and epithelium cells. In contrast, inclusion cysts gained epithelial characteristics, but lost mesenchymal characteristics. These findings support that MET occurs during the inclusion cyst formation from OSE.
大多数卵巢癌起源于卵巢的间皮表面衬里或该衬里向卵巢浅表皮质内陷形成皮质包涵囊肿。因此，这些囊肿被认为是卵巢癌的前驱病变。上皮-间质转化是一种诱导维持间充质表型的转录程序，在肿瘤进展和转移中起作用。关于间质-上皮转化（MET）的相关机制知之甚少。我们旨在通过免疫组织化学分析对人卵巢表面上皮（OSE）和包涵囊肿进行特征描述，以研究MET是否在OSE包涵囊肿形成过程中发生。我们使用了9例接受子宫切除术和双侧输卵管卵巢切除术的子宫内膜癌患者的标本。对10个含有92个包涵囊肿的正常卵巢和4个正常输卵管进行免疫组织化学分析，以检测包括钙视网膜蛋白、足板蛋白、D2-40、血栓调节蛋白、HBME-1、波形蛋白、上皮膜抗原（EMA）、WT1、癌抗原125（CA125）、MOC31、TAG-72、Ber-EP4和E-钙黏蛋白等抗原标志物的表达。正常OSE中间皮标志物的阳性染色率分别为：钙视网膜蛋白100%（10/10）、足板蛋白80%（8/10）、D2-40 80%（8/10）、血栓调节蛋白70%（7/10）、HBME-1 100%（10/10）、波形蛋白100%（10/10）。输卵管上皮中上皮标志物的阳性染色率分别为：HBME-1 100%（4/4）、波形蛋白100%（4/4）、EMA 100%（4/4）、TAG-72 75%（3/4）、Ber-EP4 100%（4/4）。包涵囊肿中两种标志物均呈阳性染色，HBME-1的发生率为51%（47/92）、波形蛋白为44%（41/92）、TAG-72为65%（60/92）、Ber-EP4为88%（81/92）。OSE表现出间充质细胞和上皮细胞的特征。相比之下，包涵囊肿获得了上皮特征，但失去了间充质特征。这些发现支持MET在OSE包涵囊肿形成过程中发生。
