Levanon Keren, Crum Christopher, Drapkin Ronny
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
J Clin Oncol. 2008 Nov 10;26(32):5284-93. doi: 10.1200/JCO.2008.18.1107. Epub 2008 Oct 14.
There are only a handful of concepts concerning cancer and carcinogenesis that are currently beyond dispute. One such dogma is the adenoma-carcinoma sequence and that a multistep accumulation of genetic alterations is required for transformation from a benign to a neoplastic tissue. The inevitable derivative of this dogma is that every invasive carcinoma is in fact a missed intraepithelial tumor, and furthermore, a late evolutionary stage in the sequence of development from a precursor lesion. Until fairly recently, high-grade serous ovarian carcinoma seemed to be one of the only known deviants of these concepts. In this article, we discuss the emergence of the fallopian tube fimbria as a field of origin for high-grade serous carcinomas and present a binary model of ovarian cancer pathogenesis that takes into consideration prior epidemiologic, morphologic, and genetic data. With the rise of the fallopian tube secretory epithelial cell as a cell of origin for high-grade pelvic serous carcinomas, the need to develop tools and model systems to characterize the biology and physiology of this cell is recognized.
目前，关于癌症和致癌作用，只有少数几个概念是毫无争议的。其中一个公认的观点是腺瘤-癌序列，即从良性组织转变为肿瘤组织需要基因改变的多步骤积累。这个观点不可避免的推论是，每一例浸润性癌实际上都是一个被漏诊的上皮内肿瘤，而且是从癌前病变发展而来的序列中的晚期进化阶段。直到最近，高级别浆液性卵巢癌似乎是这些概念中唯一已知的例外。在本文中，我们讨论了输卵管伞作为高级别浆液性癌起源部位的出现，并提出了一个卵巢癌发病机制的二元模型，该模型考虑了先前的流行病学、形态学和遗传学数据。随着输卵管分泌上皮细胞成为高级别盆腔浆液性癌的起源细胞，人们认识到需要开发工具和模型系统来表征这种细胞的生物学和生理学特性。
