Jarboe E A, Folkins A K, Drapkin R, Ince T A, Agoston E S, Crum C P
Division of Women's and Perinatal Pathology, Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Histopathology. 2008 Aug;53(2):127-38. doi: 10.1111/j.1365-2559.2007.02938.x. Epub 2008 Feb 22.
Prolongation of ovarian epithelial cancer survival depends on early detection or improved responses to chemotherapy. Gains in either have been modest at best. Understanding the diverse pathogenesis of this disease is critical to early intervention or prevention. This review addresses six important variables, including (i) cell of origin, (ii) site of origin, (iii) initial genotoxic events, (iv) risks imposed by hereditary and other promoting conditions, (v) subsequent factors that promote different patterns of metastatic spread, and (vi) prospects for intervention. This review proposes two distinct pathways to pelvic epithelial cancer. The first initiates in ovarian surface epithelium (OSE), Mullerian inclusions or endometriosis in the ovary. The second arises from the endosalpinx and encompasses a subset of serous carcinomas. The serous carcinogenic sequence in the distal fallopian tube is described and contrasted with lower grade serous tumors based on tumour location, earliest genetic change and ability (or lack of) to undergo terminal (ciliated) differentiation. Ultimately, a clear understanding of tumour origin and the mechanism(s) leading to the earliest phases of the serous and endometrioid carcinogenic sequences may hold the greatest promise for designing prevention strategies and/or developing new therapies.
延长卵巢上皮癌患者的生存期依赖于早期检测或对化疗反应的改善。然而，这两方面取得的进展都十分有限。了解这种疾病的多种发病机制对于早期干预或预防至关重要。本综述探讨了六个重要变量，包括：（i）起源细胞；（ii）起源部位；（iii）初始基因毒性事件；（iv）遗传及其他促癌条件带来的风险；（v）促进不同转移扩散模式的后续因素；（vi）干预前景。本综述提出了盆腔上皮癌的两条不同发病途径。第一条途径始于卵巢表面上皮（OSE）、苗勒氏包涵体或卵巢子宫内膜异位症。第二条途径起源于输卵管内膜，涵盖了一部分浆液性癌。文中描述了远端输卵管的浆液性致癌序列，并根据肿瘤位置、最早的基因变化以及进行终末（纤毛）分化的能力（或缺乏这种能力），将其与低级别浆液性肿瘤进行了对比。最终，清楚了解肿瘤起源以及导致浆液性和子宫内膜样致癌序列早期阶段的机制，可能为设计预防策略和/或开发新疗法带来最大的希望。
