title: STICS, SCOUTs and p53 signatures; a new language for pelvic serous carcinogenesis.
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.
authors.affiliation: Division of Women's and Perinatal Pathology, Brigham and Women's Hospital, Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Karishma
authors.initials: K
authors.lastname: Mehra
authors.forename: Mitra
authors.initials: M
authors.lastname: Mehrad
authors.forename: Geng
authors.initials: G
authors.lastname: Ning
authors.forename: Ronny
authors.initials: R
authors.lastname: Drapkin
authors.forename: Frank D
authors.initials: FD
authors.lastname: McKeon
authors.forename: Wa
authors.initials: W
authors.lastname: Xian
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Crum
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000503:physiopathology*; D005185:Fallopian Tube Neoplasms / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008954:Models, Biological; D010051:Ovarian Neoplasms / Q000235:genetics / Q000503:physiopathology*; D051762:PAX2 Transcription Factor / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D051762:PAX2 Transcription Factor; C497318:PAX2 protein, human; D016159:Tumor Suppressor Protein p53; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human