title: Secretory cell outgrowth, PAX2 and serous carcinogenesis in the Fallopian tube.
abstract: The 'p53 signature' is a benign secretory cell outgrowth in the distal Fallopian tube that shares properties with ovarian serous cancer-including p53 mutations-and is a putative serous cancer precursor. We expanded the precursor definition to all secretory cell outgrowths (SCOUTs) of 30 or more cells and scored normal (N) and altered (A) expression of both p53 and PAX2, a gene down-regulated in ovarian and endometrial cancer. SCOUTs were identified by BCL2/p73 staining in tubes from women with serous carcinoma, inherited mutations in BRCA1 or BRCA2 and controls. SCOUTs were prevalent in both proximal and distal tube and significantly associated with serous carcinoma versus the others (p < 0.001); 89% were PAX2 (A) and 26% were PAX2 (A)/p53 (A) (p53 signatures). PAX2 (A)/p53 (N) SCOUTs were free of p53 mutations; however, 12 of 13 p53 signatures were PAX2 (A). A tubal carcinoma and contiguous SCOUT were p53 (A)/PAX2 (A) and shared the same p53 mutation. SCOUTs are discretely localized alterations commonly containing altered expression of multiple genes within histologically benign tubal epithelium. Geographic distribution in the tube varies by genotype and immunophenotype, from regionally unrestricted (PAX2) to greater likelihood specific area (fimbria) of shared prevalence (PAX2 and p53). This study reveals, for the first time, an entity (SCOUT) that is associated with serous cancer, expands the topography of altered PAX2 expression in the female genital tract mucosa and highlights another potential pathway disturbance involved in early serous carcinogenesis in the Fallopian tube.
authors.affiliation: Division of Women's and Perinatal Pathology, Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Eleanor Y
authors.initials: EY
authors.lastname: Chen
authors.forename: Karishma
authors.initials: K
authors.lastname: Mehra
authors.forename: Mitra
authors.initials: M
authors.lastname: Mehrad
authors.forename: Gang
authors.initials: G
authors.lastname: Ning
authors.forename: Alexander
authors.initials: A
authors.lastname: Miron
authors.forename: George L
authors.initials: GL
authors.lastname: Mutter
authors.forename: Nicholas
authors.initials: N
authors.lastname: Monte
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Quade
authors.forename: Frank D
authors.initials: FD
authors.lastname: McKeon
authors.forename: Yosuf
authors.initials: Y
authors.lastname: Yassin
authors.forename: Wa
authors.initials: W
authors.lastname: Xian
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Crum
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005185:Fallopian Tube Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D009154:Mutation; D009363:Neoplasm Proteins / Q000378:metabolism; D051762:PAX2 Transcription Factor / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D009363:Neoplasm Proteins; D051762:PAX2 Transcription Factor; C497318:PAX2 protein, human; D016159:Tumor Suppressor Protein p53