The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory.
The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory.
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DOI：
10.1097/pas.0b013e3181cf3d79
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发表时间：
2010-03
期刊：
影响因子：
--
通讯作者：
Shih IeM
中科院分区：
文献类型：
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作者：
Kurman RJ;Shih IeM
卵巢癌是最致命的妇科恶性肿瘤。由于上皮性卵巢癌的起源和发病机制尚不清楚，早期发现和新的治疗方法以降低死亡率的努力在很大程度上是不成功的。尽管许多研究已经仔细检查了卵巢的前驱病变，但没有发现任何一项。这导致了卵巢癌从头开始发展的提议。研究表明，上皮性卵巢癌不是一种单一的疾病，而是由一组不同的肿瘤组成，这些肿瘤可以根据不同的形态和分子遗传特征进行分类。其中一组肿瘤，命名为I型，由低级别浆液性、低级别子宫内膜样癌、透明细胞癌、粘液性癌和移行(Brenner)癌组成。这些肿瘤通常表现为一种懒惰的方式，出现时局限于卵巢，作为一个群体，基因相对稳定。它们缺乏TP53的突变，但每种组织学类型都显示出独特的分子遗传学特征。此外，癌与相应的良性囊性肿瘤表现出共同的谱系，通常通过中间(交界性肿瘤)步骤，支持肿瘤进展的形态连续体。相比之下，另一组肿瘤，指定为II型，侵袭性强，进展迅速，几乎总是出现在晚期。II型肿瘤包括传统的高级别浆液性癌、未分化癌和恶性中胚叶混合瘤(癌肉瘤)。它们在80%以上的病例中显示了TP53突变，并且很少包含在I型肿瘤中发现的突变。最近的研究也提供了令人信服的证据，证明传统上被认为是原发卵巢的肿瘤实际上起源于其他盆腔器官，并继发于卵巢。因此，有人提出浆液性肿瘤是由输卵管上皮(良性或恶性)植入引起的。子宫内膜样癌和透明细胞瘤与子宫内膜异位症有关，子宫内膜异位症被认为是这些肿瘤的先兆。由于人们普遍认为子宫内膜异位症是由子宫内膜组织逆行月经发展而来的，因此有理由认为子宫内膜是这些卵巢肿瘤的来源。最后，初步数据表明粘液性和过渡性(Brenner)肿瘤是由输卵管间皮交界处的过渡型上皮巢通过化生过程产生的。对这些新概念的认识将使筛查、治疗和预防的方法更加合理，这可能会对降低这一毁灭性疾病的死亡率产生重大影响。
Ovarian cancer is the most lethal gynecologic malignancy. Efforts at early detection and new therapeutic approaches to reduce mortality have been largely unsuccessful because the origin and pathogenesis of epithelial ovarian cancer are poorly understood. Despite numerous studies that have carefully scrutinized the ovaries for precursor lesions, none have been found. This has led to the proposal that ovarian cancer develops de novo. Studies have shown that epithelial ovarian cancer is not a single disease but is composed of a diverse group of tumors that can be classified based on distinctive morphologic and molecular genetic features. One group of tumors, designated type I, is composed of low-grade serous, low-grade endometrioid, clear cell, mucinous and transitional (Brenner) carcinomas. These tumors generally behave in an indolent fashion, are confined to the ovary at presentation and, as a group, are relatively genetically stable. They lack mutations of TP53 but each histologic type exhibits a distinctive molecular genetic profile. Moreover, the carcinomas exhibit a shared lineage with the corresponding benign cystic neoplasm often through an intermediate (borderline tumor) step, supporting the morphologic continuum of tumor progression. In contrast, another group of tumors, designated type II, are highly aggressive, evolve rapidly and almost always present in advanced stage. Type II tumors include conventional high-grade serous carcinoma, undifferentiated carcinoma and malignant mixed mesodermal tumors (carcinosarcoma). They displayTP53 mutations in over 80% of cases and rarely harbor the mutations that are found in the type I tumors. Recent studies have also provided cogent evidence that what have been traditionally thought to be primary ovarian tumors actually originate in other pelvic organs and involve the ovary secondarily. Thus, it has been proposed that serous tumors arise from the implantation of epithelium (benign or malignant) from the fallopian tube. Endometrioid and clear cell tumors have been associated with endometriosis, which is regarded as the precursor of these tumors. Since it is generally accepted that endometriosis develops from endometrial tissue by retrograde menstruation it is reasonable to assume that the endometrium is the source of these ovarian neoplasms. Finally, preliminary data suggest that mucinous and transitional (Brenner) tumors arise from transitional-type epithelial nests at the tubal-mesothelial junction by a process of metaplasia. Appreciation of these new concepts will allow for a more rationale approach to screening, treatment and prevention which potentially can have a significant impact on reducing the mortality of this devastating disease.