STICS, SCOUTs and p53 signatures; a new language for pelvic serous carcinogenesis.
STICS, SCOUTs and p53 signatures; a new language for pelvic serous carcinogenesis.
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DOI：
10.2741/e275
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发表时间：
2011-01-01
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影响因子：
--
通讯作者：
Crum, Christopher P
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作者：
Mehra, Karishma;Mehrad, Mitra;Crum, Christopher P
导致最常见和最致命的卵巢癌-高级别浆液性癌-的事件一直知之甚少。然而，对生殖系BRCA 1或BRCA2 （BCRA+）突变的无症状女性的详细病理研究发现了一种早期恶性肿瘤，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纤维膜联系起来。高级别浆液性癌和子宫内膜样癌之间的区别继续缩小，pTEN、PAX2和p53的表达发生了共同的改变。此外，良性输卵管上皮中p53克隆性改变的发现- p53特征-为在纤维中发现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表达改变相关的通用分泌细胞生长（SCOUT）。随着基因改变的范围的扩大及其与浆液性癌发生的联系的明确，高级别苗勒氏癌的有力途径将出现。这将挑战关于卵巢癌发生的传统思维，但将为卵巢癌预防研究提供新的模板。
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.