Mehra Karishma, Mehrad Mitra, Ning Geng, Drapkin Ronny, McKeon Frank D, Xian Wa, Crum Christopher P
Division of Women's and Perinatal Pathology, Brigham and Women's Hospital, Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Front Biosci (Elite Ed). 2011 Jan 1;3(2):625-34. doi: 10.2741/e275.
The events leading to the most common and most lethal ovarian carcinoma - high grade serous carcinoma - have been poorly understood. However, the detailed pathologic study of asymptomatic women with germ-line BRCA 1 or BRCA2 (BCRA+) mutations has unearthed an early malignancy, serous tubal intraepithelial carcinomas (STIC), which has linked many peritoneal and ovarian serous carcinomas to the fimbria. The distinction between high-grade serous and endometrioid carcinomas continues to narrow, with shared alterations in expression of pTEN, PAX2 and p53. Moreover, the discovery of clonal alterations in p53 in benign tubal epithelium, - p53 signatures - has established a foundation for a serous cancer precursor in the fimbria. We have expanded this concept to include a generic secretory cell outgrowth (SCOUT) in the fallopian tube that is associated with altered PAX2 expression. As the repertoire of gene alterations is expanded and its link to serous carcinogenesis clarified, a cogent pathway to high-grade Mullerian carcinomas will emerge. This will challenge conventional thinking about ovarian carcinogenesis but will provide a new template for studies of ovarian cancer prevention.
导致最常见、最致命的卵巢癌——高级别浆液性癌——的发病过程一直未被充分了解。然而，对携带种系BRCA 1或BRCA2（BCRA+）突变的无症状女性进行的详细病理研究发现了一种早期恶性肿瘤，即浆液性输卵管上皮内癌（STIC），它将许多腹膜和卵巢浆液性癌与输卵管伞端联系起来。高级别浆液性癌和子宫内膜样癌之间的区别不断缩小，在PTEN、PAX2和p53的表达上存在共同改变。此外，在良性输卵管上皮中发现p53的克隆性改变——p53特征——为输卵管伞端浆液性癌前体奠定了基础。我们将这一概念扩展到包括输卵管中与PAX2表达改变相关的一种普通分泌细胞增生（SCOUT）。随着基因改变谱的扩大及其与浆液性癌发生的联系得以阐明，一条通向高级别苗勒管癌的有力途径将会出现。这将挑战关于卵巢癌发生的传统观念，但将为卵巢癌预防研究提供一个新的模板。
