Precursors and pathogenesis of ovarian carcinoma
Precursors and pathogenesis of ovarian carcinoma
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DOI：
10.1097/pat.0b013e32835f2264
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发表时间：
2013-04-01
期刊：
影响因子：
4.5
通讯作者：
Oliva, E.
中科院分区：
文献类型：
--
作者：
Lim, D.;Oliva, E.
定义癌症特异性前兆的最终目标是促进在侵袭性恶性肿瘤发生之前的早期检测和干预。与其他涉及女性生殖道的恶性肿瘤（例如宫颈癌或子宫内膜癌）不同，卵巢癌的前驱病变尚未得到很好的表征，导致未能制定有效的筛查计划。最近的临床病理学和分子研究为卵巢癌的起源和发病机制提供了新的见解。研究表明，卵巢癌由不同的肿瘤类型组成，这些肿瘤类型不仅在形态上不同，而且在发病机制、分子改变和临床进展方面也不同。已经提出了卵巢癌发生的二元模型。 I型肿瘤包括低级别浆液性癌、低级别子宫内膜样癌、透明细胞癌、粘液性癌和布伦纳肿瘤，通常是惰性的并且往往是遗传稳定的，尽管透明细胞癌可能属于中间类别。它们展示了从良性前体（例如良性肿瘤或子宫内膜异位症）的逐步进展，其特征是针对特定细胞信号传导途径的遗传畸变。 II型肿瘤包括高级别浆液性癌、高级别子宫内膜样癌和未分化癌以及恶性混合中胚层肿瘤。它们在临床上具有攻击性，并且表现出高度的遗传不稳定性和频繁的 p53 突变。越来越多的证据表明，许多高级别浆液性癌起源于远端输卵管的上皮，而浆液性输卵管上皮内癌（STIC）代表了这些肿瘤的假定前体。低度浆液性癌是通过良性和交界性浆液性肿瘤的转化而产生的，被认为源自卵巢表面或输卵管上皮的包涵囊肿。最近有人提出，乳头状输卵管增生可能是浆液性交界性肿瘤的假定前体病变。子宫内膜样癌和透明细胞癌都是由子宫内膜异位症通过影响不同遗传途径的改变而发展而来。粘液性和移行细胞肿瘤的起源尚不明确，尽管新数据表明可能起源于输卵管-间皮连接处的移行细胞巢。同样，由于癌肉瘤罕见，其发病机制也尚未明确，但越来越多的证据表明，癌性成分决定了疾病的病程并产生恶性间质成分。这篇综述讨论了卵巢癌发病机制的最新进展，特别强调了产生主要组织学亚型的假定前体病变。对这些病变的认识不仅对于提高对卵巢癌发生的认识很重要，而且还将影响我们预防、检测和治疗这些肿瘤的方法。
The ultimate goal of defining cancer specific precursors is to facilitate early detection and intervention before the development of invasive malignancy. Unlike other malignancies involving the female genital tract such as cervical or endometrial carcinomas, precursor lesions of ovarian carcinomas have not been well characterised, resulting in a failure to develop effective screening programs. Recent clinicopathological and molecular studies have provided new insight into the origin and pathogenesis of ovarian carcinomas. It has been shown that ovarian cancer is comprised of different tumour types differing not only in morphology, but also in pathogenesis, molecular alterations and clinical progression. A dualistic model of ovarian carcinogenesis has been proposed. Type I tumours which include low grade serous, low grade endometrioid, clear cell, mucinous carcinomas and Brenner tumours, are generally indolent and tend to be genetically stable, although clear cell carcinoma would probably belong to an intermediate category. They demonstrate a step-wise progression from a benign precursor such as a benign to borderline tumour or endometriosis and are characterised by genetic aberrations targeting specific cell signalling pathways. Type II tumours comprise high grade serous, high grade endometrioid, and undifferentiated carcinomas as well as malignant mixed mesodermal tumours. They are clinically aggressive and exhibit high genetic instability with frequent p53 mutations. Mounting evidence suggests that many high grade serous carcinomas originate from the epithelium of the distal fallopian tube, and that serous tubal intraepithelial carcinoma (STIC) represents the putative precursor of these neoplasms. Low grade serous carcinomas arise via transformation of benign and borderline serous tumours, thought to be derived from inclusion cysts originating from the ovarian surface or tubal epithelium. Recently it has been suggested that papillary tubal hyperplasia may be a putative precursor lesion for serous borderline tumours. Both endometrioid and clear cell carcinomas develop from endometriosis, via alterations affecting different genetic pathways. The origin of mucinous and transitional cell neoplasms is not well characterised, although new data suggest a possible origin from transitional cell nests present at the tubal-mesothelial junction. Likewise, the pathogenesis of carcinosarcomas is also not well established because of their rarity but there is accumulating evidence that the carcinomatous component determines the course of the disease and gives rise to the malignant mesenchymal component. This review discusses recent developments in the pathogenesis of ovarian carcinoma, with particular emphasis on the putative precursor lesions that give rise to the major histological subtypes. Recognition of these lesions is not only important in improving the understanding of ovarian carcinogenesis, but it will also influence our approach to prevent, detect and treat these tumours.