Open Access
Article
STICS, SCOUTs and p53 signatures; a new language for pelvic serous carcinogenesis
Karishma Mehra1,Mitra Mehrad1,Geng Ning1,Ronny Drapkin1,Frank D McKeon1,Wa Xian1,Christopher P Crum1
1
Division of Women's and Perinatal Pathology, Brigham and Women's Hospital, Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
DOI: 10.2741/E275 Volume 3 Issue 2, pp.625-634
Published: 01 January 2011
(This article belongs to the Special Issue Advances in gynecologic malignancies)
Abstract

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.

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Karishma Mehra, Mitra Mehrad, Geng Ning, Ronny Drapkin, Frank D McKeon, Wa Xian, Christopher P Crum. STICS, SCOUTs and p53 signatures; a new language for pelvic serous carcinogenesis. Frontiers in Bioscience-Elite. 2011. 3(2); 625-634.