Mesenchymal to epithelial transition in the human ovarian surface epithelium focusing on inclusion cysts

Mesenchymal to epithelial transition in the human ovarian surface epithelium focusing on inclusion cysts
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DOI:
10.3892/or_00000343
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发表时间:
2009-05-01
期刊:
影响因子:
4.2
通讯作者:
Tanaka, Tadao
Tanaka, Tadao
中科院分区:
医学3区
文献类型:
--
作者:
Okamoto, Sanshiro;Okamoto, Aikou;Tanaka, Tadao

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大多数卵巢癌起源于卵巢的间皮表面衬里或该衬里内陷到卵巢表层皮质中形成皮质包涵体囊肿。因此,这些囊肿被认为是卵巢癌的前驱病变。上皮-间充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。间充质上皮转化(MET)的机制知之甚少。我们的目的是通过免疫组织化学分析来表征人卵巢表面上皮(OSE)和包涵体囊肿,以检查MET是否发生在OSE的包涵体囊肿形成过程中。我们使用了9例子宫内膜癌患者的标本,这些患者接受了子宫切除术和双侧输卵管卵巢切除术。应用免疫组化方法检测10例正常卵巢(含92个包涵体囊肿)和4例正常输卵管组织中calretinin、podoplanin、D2-40、thrombomodulin、HBME-1、vimentin、EMA、WT 1、CA 125、MOC 31、TAG-72、Ber-EP 4和E-cadherin的表达。正常OSE组织中间皮细胞标志物的阳性表达率分别为Calretinin 100%(10/10)、Podoplanin 80%(8/10)、D2-40 80%(8/10)、Thrombomodulin 70%(7/10)、HBME-1 100%(10/10)、vimentin 100%(10/10)。输卵管上皮标记物HBME-Ⅰ、波形蛋白、EMA、TAG-72、Ber-EP-4的阳性率分别为100%(4/4)、100%(4/4)、75%(3/4)、100%(4/4)。包涵体囊肿显示两种标记物的阳性染色,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-EP 4为88%(81/92)。OSE具有间充质细胞和上皮细胞的特征。相比之下,包涵体囊肿获得上皮特征,但失去间质特征。这些发现支持MET发生在OSE形成包涵体囊肿期间。
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-I, 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.