Crum Christopher P, Drapkin Ronny, Kindelberger David, Medeiros Fabiola, Miron Alexander, Lee Yonghee
Department of Pathology, Brigham and Womens Hospital, 75 Francis Street, Boston, MA 02115, USA.
Clin Med Res. 2007 Mar;5(1):35-44. doi: 10.3121/cmr.2007.702.
Ovarian epithelial cancer is diagnosed in approximately 25,000 women yearly in the United States, accounting for approximately 12,500 deaths. Of these tumors, serous cancer is the most lethal, due to its capacity to spread beyond the reproductive tract and involve the peritoneal surfaces or distant organs. Conventional classification systems designate tumor origins principally on the location of the largest tumor. However, despite the fact that the largest tumors typically involve the ovaries, demonstrations of a precise starting point for these tumors, including precursor lesions, have been inconsistent. In recent years, a major effort to prevent serous cancer in genetically susceptible women with mutations in BRCA1 or BRCA2 has spawned the practice of prophylactic salpingo-oophorectomy. This practice has surprisingly revealed that many early cancers in these women arise in the fallopian tube, and further studies have pinpointed the distal (fimbrial) portion as the most common site of origin. Emerging studies that carefully examine the fallopian tubes suggest a high frequency of early cancer in the fimbria in unselected women with ovarian and peritoneal serous carcinoma, raising the distinct possibility that a significant proportion of these tumors have a fimbrial origin. The evidence for these discoveries and their relevance to serous cancer classification, early detection and prevention are addressed in this review. A model for pelvic serous cancer is proposed that takes into account five distinct variables which ultimately impact on origin and tumor distribution: (1) location of target epithelium, (2) genotoxic stress, (3) type of epithelium, (4) mitigating genetic factors, and (5) tumor spread pattern. Ultimately, this model illustrates the importance of identifying cancer precursors, inasmuch as these entities are useful as both surrogate endpoints for their respective malignancies in epidemiologic studies and natural targets for cancer prevention.
在美国，每年约有25000名女性被诊断出患有卵巢上皮癌，其中约12500人死亡。在这些肿瘤中，浆液性癌最为致命，因为它能够扩散到生殖道以外，累及腹膜表面或远处器官。传统的分类系统主要根据最大肿瘤的位置来确定肿瘤的起源。然而，尽管最大的肿瘤通常累及卵巢，但这些肿瘤的确切起始点，包括前驱病变，一直存在不一致的情况。近年来，为预防携带BRCA1或BRCA2基因突变的遗传易感女性患浆液性癌所做的一项重大努力催生了预防性输卵管卵巢切除术。令人惊讶的是，这种手术发现这些女性中的许多早期癌症起源于输卵管，进一步的研究已确定远端（伞端）部分是最常见的起源部位。对输卵管进行仔细检查的新研究表明，在未选择的患有卵巢和腹膜浆液性癌的女性中，输卵管伞端早期癌症的发生率很高，这增加了一个显著可能性，即这些肿瘤中有很大一部分起源于输卵管伞端。本综述探讨了这些发现的证据及其与浆液性癌分类、早期检测和预防的相关性。本文提出了一个盆腔浆液性癌模型，该模型考虑了五个不同的变量，这些变量最终会影响起源和肿瘤分布：（1）靶上皮的位置，（2）基因毒性应激，（3）上皮类型，（4）减轻遗传因素，以及（5）肿瘤扩散模式。最终，这个模型说明了识别癌症前驱病变的重要性，因为这些实体在流行病学研究中既可用作各自恶性肿瘤的替代终点，也是癌症预防的天然靶点。
